Functional organization of the Immune System

67

Transcript of Functional organization of the Immune System

Page 1: Functional organization of the Immune System

Presentation outlinePresentation outline

11 Critical functions of immune systemCritical functions of immune system

22 Dual nature Dual nature

33 CharacteristicsCharacteristics

44 FunctionsFunctions

55 Features Features

66 Mechanisms of immune response Mechanisms of immune response

77 Types of immune systems Types of immune systems

The immune system is The immune system is crucial to human crucial to human

survivalsurvivalbull The immune system consists of a The immune system consists of a

complex network of organs cells and complex network of organs cells and moleculesmolecules which work together to defend which work together to defend the body from disease causing organisms the body from disease causing organisms (bacteria viruses fungi and parasites)(bacteria viruses fungi and parasites)

bull The purpose of the immune system is The purpose of the immune system is to to maintain homeostasismaintain homeostasis which includes which includes protecting the body from pathogens and protecting the body from pathogens and toxins that could disrupt the toxins that could disrupt the homeostasishomeostasis

The Bodyrsquos DefensesThe Bodyrsquos DefensesThe Immune SystemThe Immune System

Vertebrate Immune MechanismsVertebrate Immune Mechanismsbull Innate ImmunityInnate Immunitybull Acquired ImmunityAcquired Immunitybull Cell-Mediated ResponseCell-Mediated Responsebull Humoral ResponseHumoral Responsebull Lymphatic TissuesLymphatic Tissues

Multilayered and dual nature of Multilayered and dual nature of the Immune Systemthe Immune System

The architecture of the immune system is multi-layered The architecture of the immune system is multi-layered with defenses on several levels with defenses on several levels Several barriers (external to internal simple to Several barriers (external to internal simple to complex) provided at many levels of infection complex) provided at many levels of infection The immune system has a series of dual naturesThe immune system has a series of dual natures

Self non-self recognitionSelf non-self recognitionNatural adaptiveNatural adaptiveCell mediated humoral Cell mediated humoral Passive activePassive activePrimary secondaryPrimary secondary

bull Both systems consist of a multitude of cells and Both systems consist of a multitude of cells and molecules that interact in a complex manner to detect molecules that interact in a complex manner to detect and eliminate pathogensand eliminate pathogens

Characteristics of the immune Characteristics of the immune responseresponse

11 SpecificitySpecificity the ability to distinguish the ability to distinguish between antigens between antigens

22 AdaptivenessAdaptiveness the ability to respond to the ability to respond to previously unseen moleculespreviously unseen molecules

33 Recognition of self and non-self Recognition of self and non-self the ability the ability to recognize and respond to molecules that to recognize and respond to molecules that are foreign or lsquonon-self lsquoand the molecules are foreign or lsquonon-self lsquoand the molecules that are lsquoselfrsquothat are lsquoselfrsquo

44 MemoryMemory the ability to recall previous the ability to recall previous contact with a foreign molecule and respond contact with a foreign molecule and respond to it in a learned mannerto it in a learned manner

Functions of immune Functions of immune systemsystem

bull The immune system like any organization The immune system like any organization has members that perform different has members that perform different functions to accomplish a common goalfunctions to accomplish a common goal

11 Provides defenses against pathogensProvides defenses against pathogens

22 Removes dead or worn out cells like RBCsRemoves dead or worn out cells like RBCs

33 Identifies and destroys abnormal cancer Identifies and destroys abnormal cancer cellscells

44 Protects from autoimmune diseasesProtects from autoimmune diseases

55 Rejects tissues cells of foreign antigens Rejects tissues cells of foreign antigens

Main features of Immune Main features of Immune system system

Pattern recognitionPattern recognition

(anomaly detection noise (anomaly detection noise tolerance) tolerance)

distributed No central point of distributed No central point of controlcontrol

diversity diversity

learning learning

memory memory

redundancy redundancy

robustness robustness

feature extraction feature extraction

multilayered andmultilayered and

adaptiveadaptive

Mechanism of immune Mechanism of immune responseresponse

bull The immune system specifically recognizes and The immune system specifically recognizes and selectively eliminates pathogensselectively eliminates pathogens

bull There are two critical steps in the immune There are two critical steps in the immune responseresponse11 Detection eventsDetection events22 Elimination eventsElimination events

bull The detection and elimination of pathogens The detection and elimination of pathogens depend upon the chemical bonding between depend upon the chemical bonding between receptors on the surface of an immune cell and receptors on the surface of an immune cell and epitopes found on the surface of a pathogenepitopes found on the surface of a pathogen

bull The The complementary receptor ndash epitope bindingcomplementary receptor ndash epitope binding ( monospecificity) activates a complex system ( monospecificity) activates a complex system of signalling that mediates the immune responseof signalling that mediates the immune response

Mechanism of immune Mechanism of immune responseresponse

bull Immune Immune recognition phaserecognition phase is critical in is critical in the normal functioning of the systemthe normal functioning of the system

bull This is accomplished by three sets of This is accomplished by three sets of antigen binding molecules antigen binding molecules

11 T- cell antigen receptors (TCR)T- cell antigen receptors (TCR)22 Class I and class II molecules of the Class I and class II molecules of the

MHCMHC33 B-cell antigen receptor (BCR B-cell antigen receptor (BCR

immunoglobulin)immunoglobulin)bull The The effector phaseeffector phase is mediated by a is mediated by a

variety of cells and soluble factorsvariety of cells and soluble factors

Immune SystemImmune System

Two types of immune Two types of immune systemsystem

1048698 1048698 Innate Innate immune systemimmune system

1048698 1048698 Adaptive Adaptive immune systemimmune system

Main Types of Immunity in Main Types of Immunity in ManMan

Immunity

Innate immunity

Adaptive immunity

Natural Artificial

Passive (maternal)

Active (Infection)

Passive (Serotherapy)

Active (Vaccination)

Innate ImmunityInnate Immunitybull responds immediatelyresponds immediatelybull protects the body from all foreign substancesprotects the body from all foreign substancesbull functions on two levelsfunctions on two levelsbull first line of defense ndash prevents entry of first line of defense ndash prevents entry of

pathogenspathogensbull mechanical barriersmechanical barriers

skin mucosa and secretionsskin mucosa and secretionsbull second line of defense ndash inhibits spread of second line of defense ndash inhibits spread of

pathogenpathogenbull antimicrobial proteinsantimicrobial proteinsbull phagocytes and other cellsphagocytes and other cellsbull inflammationinflammation

Three Lines of DefenseThree Lines of Defense

1st Line ndash barriers at portals of entry1st Line ndash barriers at portals of entry10486981048698primarily inborn and nonspecificprimarily inborn and nonspecific

2nd Line ndash protective cells and chemicals2nd Line ndash protective cells and chemicals10486981048698come into play when barriers are breachedcome into play when barriers are breached10486981048698primarily inborn and nonspecificprimarily inborn and nonspecific

3rd Line ndash antibodies and cytotoxic cells3rd Line ndash antibodies and cytotoxic cells10486981048698provides long-term immunity after provides long-term immunity after encountersencounters10486981048698primarily acquired and specificprimarily acquired and specific

Lines of defenseLines of defensebull 11stst lines of defense lines of defense are the physical barriers which include are the physical barriers which include

the skin urine tears ciliary elevator mucosal membrane etcthe skin urine tears ciliary elevator mucosal membrane etc

bull 22ndnd lines of defense lines of defense are the macrophage system are the macrophage system complement fever interferon and inflammation complement fever interferon and inflammation

bull 33rdrd lines of defense lines of defense aare the specific system also known re the specific system also known as acquired or adaptive immunity The specific system consists of B cells (humoral) and T cells (cell-mediated)

Physical and Chemical Physical and Chemical DefensesDefenses

First line of defense-1First line of defense-1

bull The first line of defense are The first line of defense are barrier barrier tissuestissues such as the skin that stop the such as the skin that stop the entry of pathogens into our bodiesentry of pathogens into our bodies

bull If these barrier layers are If these barrier layers are penetrated cells like penetrated cells like macrophages macrophages and neutrophilsand neutrophils engulf foreign engulf foreign organisms and kill them without the organisms and kill them without the need for antibodies need for antibodies

First Line of Defense-2First Line of Defense-2

bull SkinSkin provides an almost impenetrable provides an almost impenetrable biological barrier biological barrier

bull Lysozyme Lysozyme is an enzyme found in tears is an enzyme found in tears and saliva that and saliva that can break down foreign can break down foreign agents agents

bull The clotting of blood near open wounds The clotting of blood near open wounds prevents an open space for antigensprevents an open space for antigens

bull Mucus and cilia found in the nose and Mucus and cilia found in the nose and throat can catch foreign agents then throat can catch foreign agents then sweep them outside via sweep them outside via coughing coughing sneezing and vomiting sneezing and vomiting

bull The cell wall of plants consists of The cell wall of plants consists of fibrous fibrous proteinsproteins which provide a barrier to which provide a barrier to potential parasites (antigens) potential parasites (antigens)

A second line of defense-1A second line of defense-1

bull A second line of defense is the specific or A second line of defense is the specific or adaptive adaptive immune systemimmune system which may take days to respond which may take days to respond to a primary invasion to a primary invasion

bull The The production of antibodies and cell-mediated production of antibodies and cell-mediated responsesresponses may occur in which specific cells may occur in which specific cells recognize foreign pathogens and destroy themrecognize foreign pathogens and destroy them

bull The response is often more rapid because of the The response is often more rapid because of the activation of memory B and T cellsactivation of memory B and T cells

bull cells of the immune system interact with one cells of the immune system interact with one another by a variety of another by a variety of signal moleculessignal molecules

bull These signals may be proteins such as These signals may be proteins such as lymphokines cytokines and chemokineslymphokines cytokines and chemokines which which stimulate cells of the immune system stimulate cells of the immune system

Second Line of Defense-2Second Line of Defense-2

bull Second lines of defense deal with Second lines of defense deal with antigens that have bypassed the first antigens that have bypassed the first lines of defense lines of defense

bull InterferonsInterferons are a family of proteins that are a family of proteins that are released by a cell that is under are released by a cell that is under attack by an antigen attack by an antigen

bull One method of attacking antigens is by One method of attacking antigens is by phagocytosisphagocytosis where the contents of where the contents of the antigen are broken down by the antigen are broken down by molecules called phagocytesmolecules called phagocytes

Adaptive immunityAdaptive immunity

bull The The second levelsecond level of defence increases in of defence increases in strength and effectiveness with each strength and effectiveness with each encounter The foreign agent is recognised encounter The foreign agent is recognised in a specific manner and the immune system in a specific manner and the immune system acquires memory towards it acquires memory towards it

bull The first encounter with an antigen is The first encounter with an antigen is known as known as the primary responsethe primary response Re- Re-encounter with the same antigen causes a encounter with the same antigen causes a secondary responsesecondary response that is more rapid and that is more rapid and powerfulpowerful

Adaptive immunityAdaptive immunitybull As response produce antibodies to specific As response produce antibodies to specific

infectionsinfections

Some featuresSome features

ndash ndash MemoryMemorybull Each successive encounter with the same Each successive encounter with the same

pathogen improve the responsepathogen improve the response

ndash ndash Clonal selectionClonal selectionbull Select the best and matured immune cells Select the best and matured immune cells

to defend the organism against infectionsto defend the organism against infections

bull Whenever T cells and B cells are activated Whenever T cells and B cells are activated some become some become memory cellsmemory cells The next time The next time that an individual encounters that same that an individual encounters that same antigen the immune system is primed to antigen the immune system is primed to destroy it quickly This is destroy it quickly This is active immunityactive immunity

bull Long-term active immunityLong-term active immunity can be naturally can be naturally acquired by infection or artificially acquired acquired by infection or artificially acquired by vaccines by vaccines

bull Short-term passive immunityShort-term passive immunity can be can be transferred artificially from one individual to transferred artificially from one individual to another via antibody-rich serum another via antibody-rich serum

Active and Passive Acquired Active and Passive Acquired ImmunityImmunity

bull Active immunityActive immunity

ndash Conferred by recovery from infectious diseaseConferred by recovery from infectious disease

ndash Depends on persons own immune systemDepends on persons own immune system

ndash May be acquired artificially with May be acquired artificially with vaccinesvaccines

bull Passive immunityPassive immunity

ndash transferred from person to person through transfer of antibodiestransferred from person to person through transfer of antibodies

ndash Natural instances include antibodies passing across placenta from Natural instances include antibodies passing across placenta from mother to fetus (provides temporary protection) or through the mother to fetus (provides temporary protection) or through the milkmilk

ndash Transferred artificially Eg antibody injections for rabies anti Transferred artificially Eg antibody injections for rabies anti rhesus factor snake venom botulinun toxinrhesus factor snake venom botulinun toxin

bull Lymphatic vessels are responsible for flow of lymph Lymphatic vessels are responsible for flow of lymph within the lymphoid system within the lymphoid system

bull Plasma constantly leaks out of capillaries to deliver Plasma constantly leaks out of capillaries to deliver oxygen and nutrients to cells of the surrounding oxygen and nutrients to cells of the surrounding tissue Once in the tissue the plasma is now called tissue Once in the tissue the plasma is now called tissue fluidtissue fluid

bull While most of this tissue fluid re-enters capillaries While most of this tissue fluid re-enters capillaries and is returned directly to the bloodstream some and is returned directly to the bloodstream some fluid enters lymph vessels as fluid enters lymph vessels as lymph lymph

bull LYMPH-LYMPH- flows from the intercellular tissue spaces flows from the intercellular tissue spaces into lymphatic capillaries and then into a series of into lymphatic capillaries and then into a series of larger collecting vessels called larger collecting vessels called lymphatic vesselslymphatic vessels Lymphatic vessels converge into Lymphatic vessels converge into the thoracic ductthe thoracic duct which returns the fluid to the circulatory system by which returns the fluid to the circulatory system by dumping into the left dumping into the left subclavian vein subclavian vein

Thoracicduct

Overview of blood and lymph system and how Overview of blood and lymph system and how leukocytes travel from one system to anotherleukocytes travel from one system to another

Site of exchange between theblood and lymph systems

Lymph carrying antibodiesand immune cells collect in thoracic duct where the lymph empties back into the blood circulatory system

Immune cells travel back and forth from Immune cells travel back and forth from the blood and lymph circulatory systems the blood and lymph circulatory systems and interact with extra-vascular tissues and interact with extra-vascular tissues

in the process--in the process--extravasationextravasation

muscle

Lymphatic vessels Lymphatic vessels

The organs of the The organs of the immune system immune system

Kinds of lymphoid Kinds of lymphoid OrgansOrgans

Primarycentral lymphoid organsPrimarycentral lymphoid organs ndash bone marrow bone marrow ndash thymus thymus

Secondary peripheral lymphoid tissueSecondary peripheral lymphoid tissuendash lymph nodes lymph nodes ndash spleenspleenndash mucosa-associated lymphoid tissuemucosa-associated lymphoid tissue

Kinds of Lymphoid Organs Kinds of Lymphoid Organs The Lymphoid

Organs

Primary or Central organs

Secondary or Peripheral organs

1Bone marrow2Thymus gland3Bursa of fabricius

1Lymp nodes 2Spleen

3Diffuse lymphoid tissues

bull The The bone marrowbone marrow and the and the thymusthymus constitute constitute the primary lymphoid organsthe primary lymphoid organs

bull Both Both B-lymphocytesB-lymphocytes and and T-lymphocytesT-lymphocytes are are produced from stem cells in the bone produced from stem cells in the bone marrow marrow B-lymphocytes mature in the B-lymphocytes mature in the bone marrow while T-lymphocytes bone marrow while T-lymphocytes migrate to the thymus and mature migrate to the thymus and mature therethere

bull After maturation both B-lymphocytes and T-After maturation both B-lymphocytes and T-lymphocytes circulate through and lymphocytes circulate through and accumulate in accumulate in secondary lymphoid organssecondary lymphoid organs

bull The secondary lymphoid organs include lymph nodes The secondary lymphoid organs include lymph nodes and the spleen as well as lymphoid tissues and the spleen as well as lymphoid tissues

bull The lymphoid tissues include The lymphoid tissues include the tonsils the the tonsils the appendix the Peyers patchesappendix the Peyers patches in the lining of the in the lining of the small intestines (small intestines (gut-associated lymphoid tissue or gut-associated lymphoid tissue or GALTGALT) )

bull The lymphoid tissue found beneath the mucous The lymphoid tissue found beneath the mucous membranes of the bronchi (membranes of the bronchi (bronchial-associated bronchial-associated lymphoid tissue or BALTlymphoid tissue or BALT) )

bull The lymphatic tissue found in the mucous The lymphatic tissue found in the mucous membranes (membranes (mucosa-associated lymphoid tissue or mucosa-associated lymphoid tissue or MALTMALT))

bull The lymphatic tissue found beneath the skin (The lymphatic tissue found beneath the skin (skin-skin-associated lymphoid tissue or SALTassociated lymphoid tissue or SALT) )

Primary and SecondaryPrimary and Secondary Lymphoid organs Lymphoid organs

Primarycentral lymphoid Primarycentral lymphoid organs organs

BONE MARROWBONE MARROW is a central organ is a central organ where all the immune cells are where all the immune cells are born and only B cells mature born and only B cells mature (process termed as (process termed as B B lymphopoiesis) lymphopoiesis)

THYMUSTHYMUS is the other central organ is the other central organ in which T cells mature (in which T cells mature (T T lymphopoiesislymphopoiesis) )

The bone marrowThe bone marrow

Bone marrow is a spongy tissue found Bone marrow is a spongy tissue found within boneswithin bonesAll blood cells are produced within the bone All blood cells are produced within the bone marrowmarrowThe bone marrow of an adult produce about The bone marrow of an adult produce about three million red blood cells and 120000 three million red blood cells and 120000 white blood cells every second white blood cells every second All these cells originate from a small All these cells originate from a small population of stem cells which may be as population of stem cells which may be as few as one in a million of the bone marrow few as one in a million of the bone marrow cells cells

ThymuThymuss

bullThe thymus is an organ located in the The thymus is an organ located in the upper chestupper chest bullImmature lymphocytes leave the bone Immature lymphocytes leave the bone marrow and find their way to the thymus marrow and find their way to the thymus where they are ldquoeducatedrdquo to become where they are ldquoeducatedrdquo to become mature T-lymphocytesmature T-lymphocytes

ThymusThymusFlat bilobed organ situated above the heart Flat bilobed organ situated above the heart

and below the thyroid glandand below the thyroid gland Each lobe is surrounded by a capsule and is Each lobe is surrounded by a capsule and is

divided into lobules divided into lobules The lobules are separated from each other by The lobules are separated from each other by

strands of connective tissue called strands of connective tissue called trabeculaetrabeculae

Each lobule is organized into two Each lobule is organized into two compartments the compartments the cortex cortex (outer (outer compartment) the compartment) the medullamedulla (inner (inner compartment) compartment)

bull Cortex and Medulla are both crisscrossed by Cortex and Medulla are both crisscrossed by a a network of stromal cellsnetwork of stromal cells composed of composed of

bull loosely packed thymic epithelial cells loosely packed thymic epithelial cells bull interdigitating dendritic cells interdigitating dendritic cells bull macrophages macrophages

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 2: Functional organization of the Immune System

The immune system is The immune system is crucial to human crucial to human

survivalsurvivalbull The immune system consists of a The immune system consists of a

complex network of organs cells and complex network of organs cells and moleculesmolecules which work together to defend which work together to defend the body from disease causing organisms the body from disease causing organisms (bacteria viruses fungi and parasites)(bacteria viruses fungi and parasites)

bull The purpose of the immune system is The purpose of the immune system is to to maintain homeostasismaintain homeostasis which includes which includes protecting the body from pathogens and protecting the body from pathogens and toxins that could disrupt the toxins that could disrupt the homeostasishomeostasis

The Bodyrsquos DefensesThe Bodyrsquos DefensesThe Immune SystemThe Immune System

Vertebrate Immune MechanismsVertebrate Immune Mechanismsbull Innate ImmunityInnate Immunitybull Acquired ImmunityAcquired Immunitybull Cell-Mediated ResponseCell-Mediated Responsebull Humoral ResponseHumoral Responsebull Lymphatic TissuesLymphatic Tissues

Multilayered and dual nature of Multilayered and dual nature of the Immune Systemthe Immune System

The architecture of the immune system is multi-layered The architecture of the immune system is multi-layered with defenses on several levels with defenses on several levels Several barriers (external to internal simple to Several barriers (external to internal simple to complex) provided at many levels of infection complex) provided at many levels of infection The immune system has a series of dual naturesThe immune system has a series of dual natures

Self non-self recognitionSelf non-self recognitionNatural adaptiveNatural adaptiveCell mediated humoral Cell mediated humoral Passive activePassive activePrimary secondaryPrimary secondary

bull Both systems consist of a multitude of cells and Both systems consist of a multitude of cells and molecules that interact in a complex manner to detect molecules that interact in a complex manner to detect and eliminate pathogensand eliminate pathogens

Characteristics of the immune Characteristics of the immune responseresponse

11 SpecificitySpecificity the ability to distinguish the ability to distinguish between antigens between antigens

22 AdaptivenessAdaptiveness the ability to respond to the ability to respond to previously unseen moleculespreviously unseen molecules

33 Recognition of self and non-self Recognition of self and non-self the ability the ability to recognize and respond to molecules that to recognize and respond to molecules that are foreign or lsquonon-self lsquoand the molecules are foreign or lsquonon-self lsquoand the molecules that are lsquoselfrsquothat are lsquoselfrsquo

44 MemoryMemory the ability to recall previous the ability to recall previous contact with a foreign molecule and respond contact with a foreign molecule and respond to it in a learned mannerto it in a learned manner

Functions of immune Functions of immune systemsystem

bull The immune system like any organization The immune system like any organization has members that perform different has members that perform different functions to accomplish a common goalfunctions to accomplish a common goal

11 Provides defenses against pathogensProvides defenses against pathogens

22 Removes dead or worn out cells like RBCsRemoves dead or worn out cells like RBCs

33 Identifies and destroys abnormal cancer Identifies and destroys abnormal cancer cellscells

44 Protects from autoimmune diseasesProtects from autoimmune diseases

55 Rejects tissues cells of foreign antigens Rejects tissues cells of foreign antigens

Main features of Immune Main features of Immune system system

Pattern recognitionPattern recognition

(anomaly detection noise (anomaly detection noise tolerance) tolerance)

distributed No central point of distributed No central point of controlcontrol

diversity diversity

learning learning

memory memory

redundancy redundancy

robustness robustness

feature extraction feature extraction

multilayered andmultilayered and

adaptiveadaptive

Mechanism of immune Mechanism of immune responseresponse

bull The immune system specifically recognizes and The immune system specifically recognizes and selectively eliminates pathogensselectively eliminates pathogens

bull There are two critical steps in the immune There are two critical steps in the immune responseresponse11 Detection eventsDetection events22 Elimination eventsElimination events

bull The detection and elimination of pathogens The detection and elimination of pathogens depend upon the chemical bonding between depend upon the chemical bonding between receptors on the surface of an immune cell and receptors on the surface of an immune cell and epitopes found on the surface of a pathogenepitopes found on the surface of a pathogen

bull The The complementary receptor ndash epitope bindingcomplementary receptor ndash epitope binding ( monospecificity) activates a complex system ( monospecificity) activates a complex system of signalling that mediates the immune responseof signalling that mediates the immune response

Mechanism of immune Mechanism of immune responseresponse

bull Immune Immune recognition phaserecognition phase is critical in is critical in the normal functioning of the systemthe normal functioning of the system

bull This is accomplished by three sets of This is accomplished by three sets of antigen binding molecules antigen binding molecules

11 T- cell antigen receptors (TCR)T- cell antigen receptors (TCR)22 Class I and class II molecules of the Class I and class II molecules of the

MHCMHC33 B-cell antigen receptor (BCR B-cell antigen receptor (BCR

immunoglobulin)immunoglobulin)bull The The effector phaseeffector phase is mediated by a is mediated by a

variety of cells and soluble factorsvariety of cells and soluble factors

Immune SystemImmune System

Two types of immune Two types of immune systemsystem

1048698 1048698 Innate Innate immune systemimmune system

1048698 1048698 Adaptive Adaptive immune systemimmune system

Main Types of Immunity in Main Types of Immunity in ManMan

Immunity

Innate immunity

Adaptive immunity

Natural Artificial

Passive (maternal)

Active (Infection)

Passive (Serotherapy)

Active (Vaccination)

Innate ImmunityInnate Immunitybull responds immediatelyresponds immediatelybull protects the body from all foreign substancesprotects the body from all foreign substancesbull functions on two levelsfunctions on two levelsbull first line of defense ndash prevents entry of first line of defense ndash prevents entry of

pathogenspathogensbull mechanical barriersmechanical barriers

skin mucosa and secretionsskin mucosa and secretionsbull second line of defense ndash inhibits spread of second line of defense ndash inhibits spread of

pathogenpathogenbull antimicrobial proteinsantimicrobial proteinsbull phagocytes and other cellsphagocytes and other cellsbull inflammationinflammation

Three Lines of DefenseThree Lines of Defense

1st Line ndash barriers at portals of entry1st Line ndash barriers at portals of entry10486981048698primarily inborn and nonspecificprimarily inborn and nonspecific

2nd Line ndash protective cells and chemicals2nd Line ndash protective cells and chemicals10486981048698come into play when barriers are breachedcome into play when barriers are breached10486981048698primarily inborn and nonspecificprimarily inborn and nonspecific

3rd Line ndash antibodies and cytotoxic cells3rd Line ndash antibodies and cytotoxic cells10486981048698provides long-term immunity after provides long-term immunity after encountersencounters10486981048698primarily acquired and specificprimarily acquired and specific

Lines of defenseLines of defensebull 11stst lines of defense lines of defense are the physical barriers which include are the physical barriers which include

the skin urine tears ciliary elevator mucosal membrane etcthe skin urine tears ciliary elevator mucosal membrane etc

bull 22ndnd lines of defense lines of defense are the macrophage system are the macrophage system complement fever interferon and inflammation complement fever interferon and inflammation

bull 33rdrd lines of defense lines of defense aare the specific system also known re the specific system also known as acquired or adaptive immunity The specific system consists of B cells (humoral) and T cells (cell-mediated)

Physical and Chemical Physical and Chemical DefensesDefenses

First line of defense-1First line of defense-1

bull The first line of defense are The first line of defense are barrier barrier tissuestissues such as the skin that stop the such as the skin that stop the entry of pathogens into our bodiesentry of pathogens into our bodies

bull If these barrier layers are If these barrier layers are penetrated cells like penetrated cells like macrophages macrophages and neutrophilsand neutrophils engulf foreign engulf foreign organisms and kill them without the organisms and kill them without the need for antibodies need for antibodies

First Line of Defense-2First Line of Defense-2

bull SkinSkin provides an almost impenetrable provides an almost impenetrable biological barrier biological barrier

bull Lysozyme Lysozyme is an enzyme found in tears is an enzyme found in tears and saliva that and saliva that can break down foreign can break down foreign agents agents

bull The clotting of blood near open wounds The clotting of blood near open wounds prevents an open space for antigensprevents an open space for antigens

bull Mucus and cilia found in the nose and Mucus and cilia found in the nose and throat can catch foreign agents then throat can catch foreign agents then sweep them outside via sweep them outside via coughing coughing sneezing and vomiting sneezing and vomiting

bull The cell wall of plants consists of The cell wall of plants consists of fibrous fibrous proteinsproteins which provide a barrier to which provide a barrier to potential parasites (antigens) potential parasites (antigens)

A second line of defense-1A second line of defense-1

bull A second line of defense is the specific or A second line of defense is the specific or adaptive adaptive immune systemimmune system which may take days to respond which may take days to respond to a primary invasion to a primary invasion

bull The The production of antibodies and cell-mediated production of antibodies and cell-mediated responsesresponses may occur in which specific cells may occur in which specific cells recognize foreign pathogens and destroy themrecognize foreign pathogens and destroy them

bull The response is often more rapid because of the The response is often more rapid because of the activation of memory B and T cellsactivation of memory B and T cells

bull cells of the immune system interact with one cells of the immune system interact with one another by a variety of another by a variety of signal moleculessignal molecules

bull These signals may be proteins such as These signals may be proteins such as lymphokines cytokines and chemokineslymphokines cytokines and chemokines which which stimulate cells of the immune system stimulate cells of the immune system

Second Line of Defense-2Second Line of Defense-2

bull Second lines of defense deal with Second lines of defense deal with antigens that have bypassed the first antigens that have bypassed the first lines of defense lines of defense

bull InterferonsInterferons are a family of proteins that are a family of proteins that are released by a cell that is under are released by a cell that is under attack by an antigen attack by an antigen

bull One method of attacking antigens is by One method of attacking antigens is by phagocytosisphagocytosis where the contents of where the contents of the antigen are broken down by the antigen are broken down by molecules called phagocytesmolecules called phagocytes

Adaptive immunityAdaptive immunity

bull The The second levelsecond level of defence increases in of defence increases in strength and effectiveness with each strength and effectiveness with each encounter The foreign agent is recognised encounter The foreign agent is recognised in a specific manner and the immune system in a specific manner and the immune system acquires memory towards it acquires memory towards it

bull The first encounter with an antigen is The first encounter with an antigen is known as known as the primary responsethe primary response Re- Re-encounter with the same antigen causes a encounter with the same antigen causes a secondary responsesecondary response that is more rapid and that is more rapid and powerfulpowerful

Adaptive immunityAdaptive immunitybull As response produce antibodies to specific As response produce antibodies to specific

infectionsinfections

Some featuresSome features

ndash ndash MemoryMemorybull Each successive encounter with the same Each successive encounter with the same

pathogen improve the responsepathogen improve the response

ndash ndash Clonal selectionClonal selectionbull Select the best and matured immune cells Select the best and matured immune cells

to defend the organism against infectionsto defend the organism against infections

bull Whenever T cells and B cells are activated Whenever T cells and B cells are activated some become some become memory cellsmemory cells The next time The next time that an individual encounters that same that an individual encounters that same antigen the immune system is primed to antigen the immune system is primed to destroy it quickly This is destroy it quickly This is active immunityactive immunity

bull Long-term active immunityLong-term active immunity can be naturally can be naturally acquired by infection or artificially acquired acquired by infection or artificially acquired by vaccines by vaccines

bull Short-term passive immunityShort-term passive immunity can be can be transferred artificially from one individual to transferred artificially from one individual to another via antibody-rich serum another via antibody-rich serum

Active and Passive Acquired Active and Passive Acquired ImmunityImmunity

bull Active immunityActive immunity

ndash Conferred by recovery from infectious diseaseConferred by recovery from infectious disease

ndash Depends on persons own immune systemDepends on persons own immune system

ndash May be acquired artificially with May be acquired artificially with vaccinesvaccines

bull Passive immunityPassive immunity

ndash transferred from person to person through transfer of antibodiestransferred from person to person through transfer of antibodies

ndash Natural instances include antibodies passing across placenta from Natural instances include antibodies passing across placenta from mother to fetus (provides temporary protection) or through the mother to fetus (provides temporary protection) or through the milkmilk

ndash Transferred artificially Eg antibody injections for rabies anti Transferred artificially Eg antibody injections for rabies anti rhesus factor snake venom botulinun toxinrhesus factor snake venom botulinun toxin

bull Lymphatic vessels are responsible for flow of lymph Lymphatic vessels are responsible for flow of lymph within the lymphoid system within the lymphoid system

bull Plasma constantly leaks out of capillaries to deliver Plasma constantly leaks out of capillaries to deliver oxygen and nutrients to cells of the surrounding oxygen and nutrients to cells of the surrounding tissue Once in the tissue the plasma is now called tissue Once in the tissue the plasma is now called tissue fluidtissue fluid

bull While most of this tissue fluid re-enters capillaries While most of this tissue fluid re-enters capillaries and is returned directly to the bloodstream some and is returned directly to the bloodstream some fluid enters lymph vessels as fluid enters lymph vessels as lymph lymph

bull LYMPH-LYMPH- flows from the intercellular tissue spaces flows from the intercellular tissue spaces into lymphatic capillaries and then into a series of into lymphatic capillaries and then into a series of larger collecting vessels called larger collecting vessels called lymphatic vesselslymphatic vessels Lymphatic vessels converge into Lymphatic vessels converge into the thoracic ductthe thoracic duct which returns the fluid to the circulatory system by which returns the fluid to the circulatory system by dumping into the left dumping into the left subclavian vein subclavian vein

Thoracicduct

Overview of blood and lymph system and how Overview of blood and lymph system and how leukocytes travel from one system to anotherleukocytes travel from one system to another

Site of exchange between theblood and lymph systems

Lymph carrying antibodiesand immune cells collect in thoracic duct where the lymph empties back into the blood circulatory system

Immune cells travel back and forth from Immune cells travel back and forth from the blood and lymph circulatory systems the blood and lymph circulatory systems and interact with extra-vascular tissues and interact with extra-vascular tissues

in the process--in the process--extravasationextravasation

muscle

Lymphatic vessels Lymphatic vessels

The organs of the The organs of the immune system immune system

Kinds of lymphoid Kinds of lymphoid OrgansOrgans

Primarycentral lymphoid organsPrimarycentral lymphoid organs ndash bone marrow bone marrow ndash thymus thymus

Secondary peripheral lymphoid tissueSecondary peripheral lymphoid tissuendash lymph nodes lymph nodes ndash spleenspleenndash mucosa-associated lymphoid tissuemucosa-associated lymphoid tissue

Kinds of Lymphoid Organs Kinds of Lymphoid Organs The Lymphoid

Organs

Primary or Central organs

Secondary or Peripheral organs

1Bone marrow2Thymus gland3Bursa of fabricius

1Lymp nodes 2Spleen

3Diffuse lymphoid tissues

bull The The bone marrowbone marrow and the and the thymusthymus constitute constitute the primary lymphoid organsthe primary lymphoid organs

bull Both Both B-lymphocytesB-lymphocytes and and T-lymphocytesT-lymphocytes are are produced from stem cells in the bone produced from stem cells in the bone marrow marrow B-lymphocytes mature in the B-lymphocytes mature in the bone marrow while T-lymphocytes bone marrow while T-lymphocytes migrate to the thymus and mature migrate to the thymus and mature therethere

bull After maturation both B-lymphocytes and T-After maturation both B-lymphocytes and T-lymphocytes circulate through and lymphocytes circulate through and accumulate in accumulate in secondary lymphoid organssecondary lymphoid organs

bull The secondary lymphoid organs include lymph nodes The secondary lymphoid organs include lymph nodes and the spleen as well as lymphoid tissues and the spleen as well as lymphoid tissues

bull The lymphoid tissues include The lymphoid tissues include the tonsils the the tonsils the appendix the Peyers patchesappendix the Peyers patches in the lining of the in the lining of the small intestines (small intestines (gut-associated lymphoid tissue or gut-associated lymphoid tissue or GALTGALT) )

bull The lymphoid tissue found beneath the mucous The lymphoid tissue found beneath the mucous membranes of the bronchi (membranes of the bronchi (bronchial-associated bronchial-associated lymphoid tissue or BALTlymphoid tissue or BALT) )

bull The lymphatic tissue found in the mucous The lymphatic tissue found in the mucous membranes (membranes (mucosa-associated lymphoid tissue or mucosa-associated lymphoid tissue or MALTMALT))

bull The lymphatic tissue found beneath the skin (The lymphatic tissue found beneath the skin (skin-skin-associated lymphoid tissue or SALTassociated lymphoid tissue or SALT) )

Primary and SecondaryPrimary and Secondary Lymphoid organs Lymphoid organs

Primarycentral lymphoid Primarycentral lymphoid organs organs

BONE MARROWBONE MARROW is a central organ is a central organ where all the immune cells are where all the immune cells are born and only B cells mature born and only B cells mature (process termed as (process termed as B B lymphopoiesis) lymphopoiesis)

THYMUSTHYMUS is the other central organ is the other central organ in which T cells mature (in which T cells mature (T T lymphopoiesislymphopoiesis) )

The bone marrowThe bone marrow

Bone marrow is a spongy tissue found Bone marrow is a spongy tissue found within boneswithin bonesAll blood cells are produced within the bone All blood cells are produced within the bone marrowmarrowThe bone marrow of an adult produce about The bone marrow of an adult produce about three million red blood cells and 120000 three million red blood cells and 120000 white blood cells every second white blood cells every second All these cells originate from a small All these cells originate from a small population of stem cells which may be as population of stem cells which may be as few as one in a million of the bone marrow few as one in a million of the bone marrow cells cells

ThymuThymuss

bullThe thymus is an organ located in the The thymus is an organ located in the upper chestupper chest bullImmature lymphocytes leave the bone Immature lymphocytes leave the bone marrow and find their way to the thymus marrow and find their way to the thymus where they are ldquoeducatedrdquo to become where they are ldquoeducatedrdquo to become mature T-lymphocytesmature T-lymphocytes

ThymusThymusFlat bilobed organ situated above the heart Flat bilobed organ situated above the heart

and below the thyroid glandand below the thyroid gland Each lobe is surrounded by a capsule and is Each lobe is surrounded by a capsule and is

divided into lobules divided into lobules The lobules are separated from each other by The lobules are separated from each other by

strands of connective tissue called strands of connective tissue called trabeculaetrabeculae

Each lobule is organized into two Each lobule is organized into two compartments the compartments the cortex cortex (outer (outer compartment) the compartment) the medullamedulla (inner (inner compartment) compartment)

bull Cortex and Medulla are both crisscrossed by Cortex and Medulla are both crisscrossed by a a network of stromal cellsnetwork of stromal cells composed of composed of

bull loosely packed thymic epithelial cells loosely packed thymic epithelial cells bull interdigitating dendritic cells interdigitating dendritic cells bull macrophages macrophages

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 3: Functional organization of the Immune System

The Bodyrsquos DefensesThe Bodyrsquos DefensesThe Immune SystemThe Immune System

Vertebrate Immune MechanismsVertebrate Immune Mechanismsbull Innate ImmunityInnate Immunitybull Acquired ImmunityAcquired Immunitybull Cell-Mediated ResponseCell-Mediated Responsebull Humoral ResponseHumoral Responsebull Lymphatic TissuesLymphatic Tissues

Multilayered and dual nature of Multilayered and dual nature of the Immune Systemthe Immune System

The architecture of the immune system is multi-layered The architecture of the immune system is multi-layered with defenses on several levels with defenses on several levels Several barriers (external to internal simple to Several barriers (external to internal simple to complex) provided at many levels of infection complex) provided at many levels of infection The immune system has a series of dual naturesThe immune system has a series of dual natures

Self non-self recognitionSelf non-self recognitionNatural adaptiveNatural adaptiveCell mediated humoral Cell mediated humoral Passive activePassive activePrimary secondaryPrimary secondary

bull Both systems consist of a multitude of cells and Both systems consist of a multitude of cells and molecules that interact in a complex manner to detect molecules that interact in a complex manner to detect and eliminate pathogensand eliminate pathogens

Characteristics of the immune Characteristics of the immune responseresponse

11 SpecificitySpecificity the ability to distinguish the ability to distinguish between antigens between antigens

22 AdaptivenessAdaptiveness the ability to respond to the ability to respond to previously unseen moleculespreviously unseen molecules

33 Recognition of self and non-self Recognition of self and non-self the ability the ability to recognize and respond to molecules that to recognize and respond to molecules that are foreign or lsquonon-self lsquoand the molecules are foreign or lsquonon-self lsquoand the molecules that are lsquoselfrsquothat are lsquoselfrsquo

44 MemoryMemory the ability to recall previous the ability to recall previous contact with a foreign molecule and respond contact with a foreign molecule and respond to it in a learned mannerto it in a learned manner

Functions of immune Functions of immune systemsystem

bull The immune system like any organization The immune system like any organization has members that perform different has members that perform different functions to accomplish a common goalfunctions to accomplish a common goal

11 Provides defenses against pathogensProvides defenses against pathogens

22 Removes dead or worn out cells like RBCsRemoves dead or worn out cells like RBCs

33 Identifies and destroys abnormal cancer Identifies and destroys abnormal cancer cellscells

44 Protects from autoimmune diseasesProtects from autoimmune diseases

55 Rejects tissues cells of foreign antigens Rejects tissues cells of foreign antigens

Main features of Immune Main features of Immune system system

Pattern recognitionPattern recognition

(anomaly detection noise (anomaly detection noise tolerance) tolerance)

distributed No central point of distributed No central point of controlcontrol

diversity diversity

learning learning

memory memory

redundancy redundancy

robustness robustness

feature extraction feature extraction

multilayered andmultilayered and

adaptiveadaptive

Mechanism of immune Mechanism of immune responseresponse

bull The immune system specifically recognizes and The immune system specifically recognizes and selectively eliminates pathogensselectively eliminates pathogens

bull There are two critical steps in the immune There are two critical steps in the immune responseresponse11 Detection eventsDetection events22 Elimination eventsElimination events

bull The detection and elimination of pathogens The detection and elimination of pathogens depend upon the chemical bonding between depend upon the chemical bonding between receptors on the surface of an immune cell and receptors on the surface of an immune cell and epitopes found on the surface of a pathogenepitopes found on the surface of a pathogen

bull The The complementary receptor ndash epitope bindingcomplementary receptor ndash epitope binding ( monospecificity) activates a complex system ( monospecificity) activates a complex system of signalling that mediates the immune responseof signalling that mediates the immune response

Mechanism of immune Mechanism of immune responseresponse

bull Immune Immune recognition phaserecognition phase is critical in is critical in the normal functioning of the systemthe normal functioning of the system

bull This is accomplished by three sets of This is accomplished by three sets of antigen binding molecules antigen binding molecules

11 T- cell antigen receptors (TCR)T- cell antigen receptors (TCR)22 Class I and class II molecules of the Class I and class II molecules of the

MHCMHC33 B-cell antigen receptor (BCR B-cell antigen receptor (BCR

immunoglobulin)immunoglobulin)bull The The effector phaseeffector phase is mediated by a is mediated by a

variety of cells and soluble factorsvariety of cells and soluble factors

Immune SystemImmune System

Two types of immune Two types of immune systemsystem

1048698 1048698 Innate Innate immune systemimmune system

1048698 1048698 Adaptive Adaptive immune systemimmune system

Main Types of Immunity in Main Types of Immunity in ManMan

Immunity

Innate immunity

Adaptive immunity

Natural Artificial

Passive (maternal)

Active (Infection)

Passive (Serotherapy)

Active (Vaccination)

Innate ImmunityInnate Immunitybull responds immediatelyresponds immediatelybull protects the body from all foreign substancesprotects the body from all foreign substancesbull functions on two levelsfunctions on two levelsbull first line of defense ndash prevents entry of first line of defense ndash prevents entry of

pathogenspathogensbull mechanical barriersmechanical barriers

skin mucosa and secretionsskin mucosa and secretionsbull second line of defense ndash inhibits spread of second line of defense ndash inhibits spread of

pathogenpathogenbull antimicrobial proteinsantimicrobial proteinsbull phagocytes and other cellsphagocytes and other cellsbull inflammationinflammation

Three Lines of DefenseThree Lines of Defense

1st Line ndash barriers at portals of entry1st Line ndash barriers at portals of entry10486981048698primarily inborn and nonspecificprimarily inborn and nonspecific

2nd Line ndash protective cells and chemicals2nd Line ndash protective cells and chemicals10486981048698come into play when barriers are breachedcome into play when barriers are breached10486981048698primarily inborn and nonspecificprimarily inborn and nonspecific

3rd Line ndash antibodies and cytotoxic cells3rd Line ndash antibodies and cytotoxic cells10486981048698provides long-term immunity after provides long-term immunity after encountersencounters10486981048698primarily acquired and specificprimarily acquired and specific

Lines of defenseLines of defensebull 11stst lines of defense lines of defense are the physical barriers which include are the physical barriers which include

the skin urine tears ciliary elevator mucosal membrane etcthe skin urine tears ciliary elevator mucosal membrane etc

bull 22ndnd lines of defense lines of defense are the macrophage system are the macrophage system complement fever interferon and inflammation complement fever interferon and inflammation

bull 33rdrd lines of defense lines of defense aare the specific system also known re the specific system also known as acquired or adaptive immunity The specific system consists of B cells (humoral) and T cells (cell-mediated)

Physical and Chemical Physical and Chemical DefensesDefenses

First line of defense-1First line of defense-1

bull The first line of defense are The first line of defense are barrier barrier tissuestissues such as the skin that stop the such as the skin that stop the entry of pathogens into our bodiesentry of pathogens into our bodies

bull If these barrier layers are If these barrier layers are penetrated cells like penetrated cells like macrophages macrophages and neutrophilsand neutrophils engulf foreign engulf foreign organisms and kill them without the organisms and kill them without the need for antibodies need for antibodies

First Line of Defense-2First Line of Defense-2

bull SkinSkin provides an almost impenetrable provides an almost impenetrable biological barrier biological barrier

bull Lysozyme Lysozyme is an enzyme found in tears is an enzyme found in tears and saliva that and saliva that can break down foreign can break down foreign agents agents

bull The clotting of blood near open wounds The clotting of blood near open wounds prevents an open space for antigensprevents an open space for antigens

bull Mucus and cilia found in the nose and Mucus and cilia found in the nose and throat can catch foreign agents then throat can catch foreign agents then sweep them outside via sweep them outside via coughing coughing sneezing and vomiting sneezing and vomiting

bull The cell wall of plants consists of The cell wall of plants consists of fibrous fibrous proteinsproteins which provide a barrier to which provide a barrier to potential parasites (antigens) potential parasites (antigens)

A second line of defense-1A second line of defense-1

bull A second line of defense is the specific or A second line of defense is the specific or adaptive adaptive immune systemimmune system which may take days to respond which may take days to respond to a primary invasion to a primary invasion

bull The The production of antibodies and cell-mediated production of antibodies and cell-mediated responsesresponses may occur in which specific cells may occur in which specific cells recognize foreign pathogens and destroy themrecognize foreign pathogens and destroy them

bull The response is often more rapid because of the The response is often more rapid because of the activation of memory B and T cellsactivation of memory B and T cells

bull cells of the immune system interact with one cells of the immune system interact with one another by a variety of another by a variety of signal moleculessignal molecules

bull These signals may be proteins such as These signals may be proteins such as lymphokines cytokines and chemokineslymphokines cytokines and chemokines which which stimulate cells of the immune system stimulate cells of the immune system

Second Line of Defense-2Second Line of Defense-2

bull Second lines of defense deal with Second lines of defense deal with antigens that have bypassed the first antigens that have bypassed the first lines of defense lines of defense

bull InterferonsInterferons are a family of proteins that are a family of proteins that are released by a cell that is under are released by a cell that is under attack by an antigen attack by an antigen

bull One method of attacking antigens is by One method of attacking antigens is by phagocytosisphagocytosis where the contents of where the contents of the antigen are broken down by the antigen are broken down by molecules called phagocytesmolecules called phagocytes

Adaptive immunityAdaptive immunity

bull The The second levelsecond level of defence increases in of defence increases in strength and effectiveness with each strength and effectiveness with each encounter The foreign agent is recognised encounter The foreign agent is recognised in a specific manner and the immune system in a specific manner and the immune system acquires memory towards it acquires memory towards it

bull The first encounter with an antigen is The first encounter with an antigen is known as known as the primary responsethe primary response Re- Re-encounter with the same antigen causes a encounter with the same antigen causes a secondary responsesecondary response that is more rapid and that is more rapid and powerfulpowerful

Adaptive immunityAdaptive immunitybull As response produce antibodies to specific As response produce antibodies to specific

infectionsinfections

Some featuresSome features

ndash ndash MemoryMemorybull Each successive encounter with the same Each successive encounter with the same

pathogen improve the responsepathogen improve the response

ndash ndash Clonal selectionClonal selectionbull Select the best and matured immune cells Select the best and matured immune cells

to defend the organism against infectionsto defend the organism against infections

bull Whenever T cells and B cells are activated Whenever T cells and B cells are activated some become some become memory cellsmemory cells The next time The next time that an individual encounters that same that an individual encounters that same antigen the immune system is primed to antigen the immune system is primed to destroy it quickly This is destroy it quickly This is active immunityactive immunity

bull Long-term active immunityLong-term active immunity can be naturally can be naturally acquired by infection or artificially acquired acquired by infection or artificially acquired by vaccines by vaccines

bull Short-term passive immunityShort-term passive immunity can be can be transferred artificially from one individual to transferred artificially from one individual to another via antibody-rich serum another via antibody-rich serum

Active and Passive Acquired Active and Passive Acquired ImmunityImmunity

bull Active immunityActive immunity

ndash Conferred by recovery from infectious diseaseConferred by recovery from infectious disease

ndash Depends on persons own immune systemDepends on persons own immune system

ndash May be acquired artificially with May be acquired artificially with vaccinesvaccines

bull Passive immunityPassive immunity

ndash transferred from person to person through transfer of antibodiestransferred from person to person through transfer of antibodies

ndash Natural instances include antibodies passing across placenta from Natural instances include antibodies passing across placenta from mother to fetus (provides temporary protection) or through the mother to fetus (provides temporary protection) or through the milkmilk

ndash Transferred artificially Eg antibody injections for rabies anti Transferred artificially Eg antibody injections for rabies anti rhesus factor snake venom botulinun toxinrhesus factor snake venom botulinun toxin

bull Lymphatic vessels are responsible for flow of lymph Lymphatic vessels are responsible for flow of lymph within the lymphoid system within the lymphoid system

bull Plasma constantly leaks out of capillaries to deliver Plasma constantly leaks out of capillaries to deliver oxygen and nutrients to cells of the surrounding oxygen and nutrients to cells of the surrounding tissue Once in the tissue the plasma is now called tissue Once in the tissue the plasma is now called tissue fluidtissue fluid

bull While most of this tissue fluid re-enters capillaries While most of this tissue fluid re-enters capillaries and is returned directly to the bloodstream some and is returned directly to the bloodstream some fluid enters lymph vessels as fluid enters lymph vessels as lymph lymph

bull LYMPH-LYMPH- flows from the intercellular tissue spaces flows from the intercellular tissue spaces into lymphatic capillaries and then into a series of into lymphatic capillaries and then into a series of larger collecting vessels called larger collecting vessels called lymphatic vesselslymphatic vessels Lymphatic vessels converge into Lymphatic vessels converge into the thoracic ductthe thoracic duct which returns the fluid to the circulatory system by which returns the fluid to the circulatory system by dumping into the left dumping into the left subclavian vein subclavian vein

Thoracicduct

Overview of blood and lymph system and how Overview of blood and lymph system and how leukocytes travel from one system to anotherleukocytes travel from one system to another

Site of exchange between theblood and lymph systems

Lymph carrying antibodiesand immune cells collect in thoracic duct where the lymph empties back into the blood circulatory system

Immune cells travel back and forth from Immune cells travel back and forth from the blood and lymph circulatory systems the blood and lymph circulatory systems and interact with extra-vascular tissues and interact with extra-vascular tissues

in the process--in the process--extravasationextravasation

muscle

Lymphatic vessels Lymphatic vessels

The organs of the The organs of the immune system immune system

Kinds of lymphoid Kinds of lymphoid OrgansOrgans

Primarycentral lymphoid organsPrimarycentral lymphoid organs ndash bone marrow bone marrow ndash thymus thymus

Secondary peripheral lymphoid tissueSecondary peripheral lymphoid tissuendash lymph nodes lymph nodes ndash spleenspleenndash mucosa-associated lymphoid tissuemucosa-associated lymphoid tissue

Kinds of Lymphoid Organs Kinds of Lymphoid Organs The Lymphoid

Organs

Primary or Central organs

Secondary or Peripheral organs

1Bone marrow2Thymus gland3Bursa of fabricius

1Lymp nodes 2Spleen

3Diffuse lymphoid tissues

bull The The bone marrowbone marrow and the and the thymusthymus constitute constitute the primary lymphoid organsthe primary lymphoid organs

bull Both Both B-lymphocytesB-lymphocytes and and T-lymphocytesT-lymphocytes are are produced from stem cells in the bone produced from stem cells in the bone marrow marrow B-lymphocytes mature in the B-lymphocytes mature in the bone marrow while T-lymphocytes bone marrow while T-lymphocytes migrate to the thymus and mature migrate to the thymus and mature therethere

bull After maturation both B-lymphocytes and T-After maturation both B-lymphocytes and T-lymphocytes circulate through and lymphocytes circulate through and accumulate in accumulate in secondary lymphoid organssecondary lymphoid organs

bull The secondary lymphoid organs include lymph nodes The secondary lymphoid organs include lymph nodes and the spleen as well as lymphoid tissues and the spleen as well as lymphoid tissues

bull The lymphoid tissues include The lymphoid tissues include the tonsils the the tonsils the appendix the Peyers patchesappendix the Peyers patches in the lining of the in the lining of the small intestines (small intestines (gut-associated lymphoid tissue or gut-associated lymphoid tissue or GALTGALT) )

bull The lymphoid tissue found beneath the mucous The lymphoid tissue found beneath the mucous membranes of the bronchi (membranes of the bronchi (bronchial-associated bronchial-associated lymphoid tissue or BALTlymphoid tissue or BALT) )

bull The lymphatic tissue found in the mucous The lymphatic tissue found in the mucous membranes (membranes (mucosa-associated lymphoid tissue or mucosa-associated lymphoid tissue or MALTMALT))

bull The lymphatic tissue found beneath the skin (The lymphatic tissue found beneath the skin (skin-skin-associated lymphoid tissue or SALTassociated lymphoid tissue or SALT) )

Primary and SecondaryPrimary and Secondary Lymphoid organs Lymphoid organs

Primarycentral lymphoid Primarycentral lymphoid organs organs

BONE MARROWBONE MARROW is a central organ is a central organ where all the immune cells are where all the immune cells are born and only B cells mature born and only B cells mature (process termed as (process termed as B B lymphopoiesis) lymphopoiesis)

THYMUSTHYMUS is the other central organ is the other central organ in which T cells mature (in which T cells mature (T T lymphopoiesislymphopoiesis) )

The bone marrowThe bone marrow

Bone marrow is a spongy tissue found Bone marrow is a spongy tissue found within boneswithin bonesAll blood cells are produced within the bone All blood cells are produced within the bone marrowmarrowThe bone marrow of an adult produce about The bone marrow of an adult produce about three million red blood cells and 120000 three million red blood cells and 120000 white blood cells every second white blood cells every second All these cells originate from a small All these cells originate from a small population of stem cells which may be as population of stem cells which may be as few as one in a million of the bone marrow few as one in a million of the bone marrow cells cells

ThymuThymuss

bullThe thymus is an organ located in the The thymus is an organ located in the upper chestupper chest bullImmature lymphocytes leave the bone Immature lymphocytes leave the bone marrow and find their way to the thymus marrow and find their way to the thymus where they are ldquoeducatedrdquo to become where they are ldquoeducatedrdquo to become mature T-lymphocytesmature T-lymphocytes

ThymusThymusFlat bilobed organ situated above the heart Flat bilobed organ situated above the heart

and below the thyroid glandand below the thyroid gland Each lobe is surrounded by a capsule and is Each lobe is surrounded by a capsule and is

divided into lobules divided into lobules The lobules are separated from each other by The lobules are separated from each other by

strands of connective tissue called strands of connective tissue called trabeculaetrabeculae

Each lobule is organized into two Each lobule is organized into two compartments the compartments the cortex cortex (outer (outer compartment) the compartment) the medullamedulla (inner (inner compartment) compartment)

bull Cortex and Medulla are both crisscrossed by Cortex and Medulla are both crisscrossed by a a network of stromal cellsnetwork of stromal cells composed of composed of

bull loosely packed thymic epithelial cells loosely packed thymic epithelial cells bull interdigitating dendritic cells interdigitating dendritic cells bull macrophages macrophages

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 4: Functional organization of the Immune System

Multilayered and dual nature of Multilayered and dual nature of the Immune Systemthe Immune System

The architecture of the immune system is multi-layered The architecture of the immune system is multi-layered with defenses on several levels with defenses on several levels Several barriers (external to internal simple to Several barriers (external to internal simple to complex) provided at many levels of infection complex) provided at many levels of infection The immune system has a series of dual naturesThe immune system has a series of dual natures

Self non-self recognitionSelf non-self recognitionNatural adaptiveNatural adaptiveCell mediated humoral Cell mediated humoral Passive activePassive activePrimary secondaryPrimary secondary

bull Both systems consist of a multitude of cells and Both systems consist of a multitude of cells and molecules that interact in a complex manner to detect molecules that interact in a complex manner to detect and eliminate pathogensand eliminate pathogens

Characteristics of the immune Characteristics of the immune responseresponse

11 SpecificitySpecificity the ability to distinguish the ability to distinguish between antigens between antigens

22 AdaptivenessAdaptiveness the ability to respond to the ability to respond to previously unseen moleculespreviously unseen molecules

33 Recognition of self and non-self Recognition of self and non-self the ability the ability to recognize and respond to molecules that to recognize and respond to molecules that are foreign or lsquonon-self lsquoand the molecules are foreign or lsquonon-self lsquoand the molecules that are lsquoselfrsquothat are lsquoselfrsquo

44 MemoryMemory the ability to recall previous the ability to recall previous contact with a foreign molecule and respond contact with a foreign molecule and respond to it in a learned mannerto it in a learned manner

Functions of immune Functions of immune systemsystem

bull The immune system like any organization The immune system like any organization has members that perform different has members that perform different functions to accomplish a common goalfunctions to accomplish a common goal

11 Provides defenses against pathogensProvides defenses against pathogens

22 Removes dead or worn out cells like RBCsRemoves dead or worn out cells like RBCs

33 Identifies and destroys abnormal cancer Identifies and destroys abnormal cancer cellscells

44 Protects from autoimmune diseasesProtects from autoimmune diseases

55 Rejects tissues cells of foreign antigens Rejects tissues cells of foreign antigens

Main features of Immune Main features of Immune system system

Pattern recognitionPattern recognition

(anomaly detection noise (anomaly detection noise tolerance) tolerance)

distributed No central point of distributed No central point of controlcontrol

diversity diversity

learning learning

memory memory

redundancy redundancy

robustness robustness

feature extraction feature extraction

multilayered andmultilayered and

adaptiveadaptive

Mechanism of immune Mechanism of immune responseresponse

bull The immune system specifically recognizes and The immune system specifically recognizes and selectively eliminates pathogensselectively eliminates pathogens

bull There are two critical steps in the immune There are two critical steps in the immune responseresponse11 Detection eventsDetection events22 Elimination eventsElimination events

bull The detection and elimination of pathogens The detection and elimination of pathogens depend upon the chemical bonding between depend upon the chemical bonding between receptors on the surface of an immune cell and receptors on the surface of an immune cell and epitopes found on the surface of a pathogenepitopes found on the surface of a pathogen

bull The The complementary receptor ndash epitope bindingcomplementary receptor ndash epitope binding ( monospecificity) activates a complex system ( monospecificity) activates a complex system of signalling that mediates the immune responseof signalling that mediates the immune response

Mechanism of immune Mechanism of immune responseresponse

bull Immune Immune recognition phaserecognition phase is critical in is critical in the normal functioning of the systemthe normal functioning of the system

bull This is accomplished by three sets of This is accomplished by three sets of antigen binding molecules antigen binding molecules

11 T- cell antigen receptors (TCR)T- cell antigen receptors (TCR)22 Class I and class II molecules of the Class I and class II molecules of the

MHCMHC33 B-cell antigen receptor (BCR B-cell antigen receptor (BCR

immunoglobulin)immunoglobulin)bull The The effector phaseeffector phase is mediated by a is mediated by a

variety of cells and soluble factorsvariety of cells and soluble factors

Immune SystemImmune System

Two types of immune Two types of immune systemsystem

1048698 1048698 Innate Innate immune systemimmune system

1048698 1048698 Adaptive Adaptive immune systemimmune system

Main Types of Immunity in Main Types of Immunity in ManMan

Immunity

Innate immunity

Adaptive immunity

Natural Artificial

Passive (maternal)

Active (Infection)

Passive (Serotherapy)

Active (Vaccination)

Innate ImmunityInnate Immunitybull responds immediatelyresponds immediatelybull protects the body from all foreign substancesprotects the body from all foreign substancesbull functions on two levelsfunctions on two levelsbull first line of defense ndash prevents entry of first line of defense ndash prevents entry of

pathogenspathogensbull mechanical barriersmechanical barriers

skin mucosa and secretionsskin mucosa and secretionsbull second line of defense ndash inhibits spread of second line of defense ndash inhibits spread of

pathogenpathogenbull antimicrobial proteinsantimicrobial proteinsbull phagocytes and other cellsphagocytes and other cellsbull inflammationinflammation

Three Lines of DefenseThree Lines of Defense

1st Line ndash barriers at portals of entry1st Line ndash barriers at portals of entry10486981048698primarily inborn and nonspecificprimarily inborn and nonspecific

2nd Line ndash protective cells and chemicals2nd Line ndash protective cells and chemicals10486981048698come into play when barriers are breachedcome into play when barriers are breached10486981048698primarily inborn and nonspecificprimarily inborn and nonspecific

3rd Line ndash antibodies and cytotoxic cells3rd Line ndash antibodies and cytotoxic cells10486981048698provides long-term immunity after provides long-term immunity after encountersencounters10486981048698primarily acquired and specificprimarily acquired and specific

Lines of defenseLines of defensebull 11stst lines of defense lines of defense are the physical barriers which include are the physical barriers which include

the skin urine tears ciliary elevator mucosal membrane etcthe skin urine tears ciliary elevator mucosal membrane etc

bull 22ndnd lines of defense lines of defense are the macrophage system are the macrophage system complement fever interferon and inflammation complement fever interferon and inflammation

bull 33rdrd lines of defense lines of defense aare the specific system also known re the specific system also known as acquired or adaptive immunity The specific system consists of B cells (humoral) and T cells (cell-mediated)

Physical and Chemical Physical and Chemical DefensesDefenses

First line of defense-1First line of defense-1

bull The first line of defense are The first line of defense are barrier barrier tissuestissues such as the skin that stop the such as the skin that stop the entry of pathogens into our bodiesentry of pathogens into our bodies

bull If these barrier layers are If these barrier layers are penetrated cells like penetrated cells like macrophages macrophages and neutrophilsand neutrophils engulf foreign engulf foreign organisms and kill them without the organisms and kill them without the need for antibodies need for antibodies

First Line of Defense-2First Line of Defense-2

bull SkinSkin provides an almost impenetrable provides an almost impenetrable biological barrier biological barrier

bull Lysozyme Lysozyme is an enzyme found in tears is an enzyme found in tears and saliva that and saliva that can break down foreign can break down foreign agents agents

bull The clotting of blood near open wounds The clotting of blood near open wounds prevents an open space for antigensprevents an open space for antigens

bull Mucus and cilia found in the nose and Mucus and cilia found in the nose and throat can catch foreign agents then throat can catch foreign agents then sweep them outside via sweep them outside via coughing coughing sneezing and vomiting sneezing and vomiting

bull The cell wall of plants consists of The cell wall of plants consists of fibrous fibrous proteinsproteins which provide a barrier to which provide a barrier to potential parasites (antigens) potential parasites (antigens)

A second line of defense-1A second line of defense-1

bull A second line of defense is the specific or A second line of defense is the specific or adaptive adaptive immune systemimmune system which may take days to respond which may take days to respond to a primary invasion to a primary invasion

bull The The production of antibodies and cell-mediated production of antibodies and cell-mediated responsesresponses may occur in which specific cells may occur in which specific cells recognize foreign pathogens and destroy themrecognize foreign pathogens and destroy them

bull The response is often more rapid because of the The response is often more rapid because of the activation of memory B and T cellsactivation of memory B and T cells

bull cells of the immune system interact with one cells of the immune system interact with one another by a variety of another by a variety of signal moleculessignal molecules

bull These signals may be proteins such as These signals may be proteins such as lymphokines cytokines and chemokineslymphokines cytokines and chemokines which which stimulate cells of the immune system stimulate cells of the immune system

Second Line of Defense-2Second Line of Defense-2

bull Second lines of defense deal with Second lines of defense deal with antigens that have bypassed the first antigens that have bypassed the first lines of defense lines of defense

bull InterferonsInterferons are a family of proteins that are a family of proteins that are released by a cell that is under are released by a cell that is under attack by an antigen attack by an antigen

bull One method of attacking antigens is by One method of attacking antigens is by phagocytosisphagocytosis where the contents of where the contents of the antigen are broken down by the antigen are broken down by molecules called phagocytesmolecules called phagocytes

Adaptive immunityAdaptive immunity

bull The The second levelsecond level of defence increases in of defence increases in strength and effectiveness with each strength and effectiveness with each encounter The foreign agent is recognised encounter The foreign agent is recognised in a specific manner and the immune system in a specific manner and the immune system acquires memory towards it acquires memory towards it

bull The first encounter with an antigen is The first encounter with an antigen is known as known as the primary responsethe primary response Re- Re-encounter with the same antigen causes a encounter with the same antigen causes a secondary responsesecondary response that is more rapid and that is more rapid and powerfulpowerful

Adaptive immunityAdaptive immunitybull As response produce antibodies to specific As response produce antibodies to specific

infectionsinfections

Some featuresSome features

ndash ndash MemoryMemorybull Each successive encounter with the same Each successive encounter with the same

pathogen improve the responsepathogen improve the response

ndash ndash Clonal selectionClonal selectionbull Select the best and matured immune cells Select the best and matured immune cells

to defend the organism against infectionsto defend the organism against infections

bull Whenever T cells and B cells are activated Whenever T cells and B cells are activated some become some become memory cellsmemory cells The next time The next time that an individual encounters that same that an individual encounters that same antigen the immune system is primed to antigen the immune system is primed to destroy it quickly This is destroy it quickly This is active immunityactive immunity

bull Long-term active immunityLong-term active immunity can be naturally can be naturally acquired by infection or artificially acquired acquired by infection or artificially acquired by vaccines by vaccines

bull Short-term passive immunityShort-term passive immunity can be can be transferred artificially from one individual to transferred artificially from one individual to another via antibody-rich serum another via antibody-rich serum

Active and Passive Acquired Active and Passive Acquired ImmunityImmunity

bull Active immunityActive immunity

ndash Conferred by recovery from infectious diseaseConferred by recovery from infectious disease

ndash Depends on persons own immune systemDepends on persons own immune system

ndash May be acquired artificially with May be acquired artificially with vaccinesvaccines

bull Passive immunityPassive immunity

ndash transferred from person to person through transfer of antibodiestransferred from person to person through transfer of antibodies

ndash Natural instances include antibodies passing across placenta from Natural instances include antibodies passing across placenta from mother to fetus (provides temporary protection) or through the mother to fetus (provides temporary protection) or through the milkmilk

ndash Transferred artificially Eg antibody injections for rabies anti Transferred artificially Eg antibody injections for rabies anti rhesus factor snake venom botulinun toxinrhesus factor snake venom botulinun toxin

bull Lymphatic vessels are responsible for flow of lymph Lymphatic vessels are responsible for flow of lymph within the lymphoid system within the lymphoid system

bull Plasma constantly leaks out of capillaries to deliver Plasma constantly leaks out of capillaries to deliver oxygen and nutrients to cells of the surrounding oxygen and nutrients to cells of the surrounding tissue Once in the tissue the plasma is now called tissue Once in the tissue the plasma is now called tissue fluidtissue fluid

bull While most of this tissue fluid re-enters capillaries While most of this tissue fluid re-enters capillaries and is returned directly to the bloodstream some and is returned directly to the bloodstream some fluid enters lymph vessels as fluid enters lymph vessels as lymph lymph

bull LYMPH-LYMPH- flows from the intercellular tissue spaces flows from the intercellular tissue spaces into lymphatic capillaries and then into a series of into lymphatic capillaries and then into a series of larger collecting vessels called larger collecting vessels called lymphatic vesselslymphatic vessels Lymphatic vessels converge into Lymphatic vessels converge into the thoracic ductthe thoracic duct which returns the fluid to the circulatory system by which returns the fluid to the circulatory system by dumping into the left dumping into the left subclavian vein subclavian vein

Thoracicduct

Overview of blood and lymph system and how Overview of blood and lymph system and how leukocytes travel from one system to anotherleukocytes travel from one system to another

Site of exchange between theblood and lymph systems

Lymph carrying antibodiesand immune cells collect in thoracic duct where the lymph empties back into the blood circulatory system

Immune cells travel back and forth from Immune cells travel back and forth from the blood and lymph circulatory systems the blood and lymph circulatory systems and interact with extra-vascular tissues and interact with extra-vascular tissues

in the process--in the process--extravasationextravasation

muscle

Lymphatic vessels Lymphatic vessels

The organs of the The organs of the immune system immune system

Kinds of lymphoid Kinds of lymphoid OrgansOrgans

Primarycentral lymphoid organsPrimarycentral lymphoid organs ndash bone marrow bone marrow ndash thymus thymus

Secondary peripheral lymphoid tissueSecondary peripheral lymphoid tissuendash lymph nodes lymph nodes ndash spleenspleenndash mucosa-associated lymphoid tissuemucosa-associated lymphoid tissue

Kinds of Lymphoid Organs Kinds of Lymphoid Organs The Lymphoid

Organs

Primary or Central organs

Secondary or Peripheral organs

1Bone marrow2Thymus gland3Bursa of fabricius

1Lymp nodes 2Spleen

3Diffuse lymphoid tissues

bull The The bone marrowbone marrow and the and the thymusthymus constitute constitute the primary lymphoid organsthe primary lymphoid organs

bull Both Both B-lymphocytesB-lymphocytes and and T-lymphocytesT-lymphocytes are are produced from stem cells in the bone produced from stem cells in the bone marrow marrow B-lymphocytes mature in the B-lymphocytes mature in the bone marrow while T-lymphocytes bone marrow while T-lymphocytes migrate to the thymus and mature migrate to the thymus and mature therethere

bull After maturation both B-lymphocytes and T-After maturation both B-lymphocytes and T-lymphocytes circulate through and lymphocytes circulate through and accumulate in accumulate in secondary lymphoid organssecondary lymphoid organs

bull The secondary lymphoid organs include lymph nodes The secondary lymphoid organs include lymph nodes and the spleen as well as lymphoid tissues and the spleen as well as lymphoid tissues

bull The lymphoid tissues include The lymphoid tissues include the tonsils the the tonsils the appendix the Peyers patchesappendix the Peyers patches in the lining of the in the lining of the small intestines (small intestines (gut-associated lymphoid tissue or gut-associated lymphoid tissue or GALTGALT) )

bull The lymphoid tissue found beneath the mucous The lymphoid tissue found beneath the mucous membranes of the bronchi (membranes of the bronchi (bronchial-associated bronchial-associated lymphoid tissue or BALTlymphoid tissue or BALT) )

bull The lymphatic tissue found in the mucous The lymphatic tissue found in the mucous membranes (membranes (mucosa-associated lymphoid tissue or mucosa-associated lymphoid tissue or MALTMALT))

bull The lymphatic tissue found beneath the skin (The lymphatic tissue found beneath the skin (skin-skin-associated lymphoid tissue or SALTassociated lymphoid tissue or SALT) )

Primary and SecondaryPrimary and Secondary Lymphoid organs Lymphoid organs

Primarycentral lymphoid Primarycentral lymphoid organs organs

BONE MARROWBONE MARROW is a central organ is a central organ where all the immune cells are where all the immune cells are born and only B cells mature born and only B cells mature (process termed as (process termed as B B lymphopoiesis) lymphopoiesis)

THYMUSTHYMUS is the other central organ is the other central organ in which T cells mature (in which T cells mature (T T lymphopoiesislymphopoiesis) )

The bone marrowThe bone marrow

Bone marrow is a spongy tissue found Bone marrow is a spongy tissue found within boneswithin bonesAll blood cells are produced within the bone All blood cells are produced within the bone marrowmarrowThe bone marrow of an adult produce about The bone marrow of an adult produce about three million red blood cells and 120000 three million red blood cells and 120000 white blood cells every second white blood cells every second All these cells originate from a small All these cells originate from a small population of stem cells which may be as population of stem cells which may be as few as one in a million of the bone marrow few as one in a million of the bone marrow cells cells

ThymuThymuss

bullThe thymus is an organ located in the The thymus is an organ located in the upper chestupper chest bullImmature lymphocytes leave the bone Immature lymphocytes leave the bone marrow and find their way to the thymus marrow and find their way to the thymus where they are ldquoeducatedrdquo to become where they are ldquoeducatedrdquo to become mature T-lymphocytesmature T-lymphocytes

ThymusThymusFlat bilobed organ situated above the heart Flat bilobed organ situated above the heart

and below the thyroid glandand below the thyroid gland Each lobe is surrounded by a capsule and is Each lobe is surrounded by a capsule and is

divided into lobules divided into lobules The lobules are separated from each other by The lobules are separated from each other by

strands of connective tissue called strands of connective tissue called trabeculaetrabeculae

Each lobule is organized into two Each lobule is organized into two compartments the compartments the cortex cortex (outer (outer compartment) the compartment) the medullamedulla (inner (inner compartment) compartment)

bull Cortex and Medulla are both crisscrossed by Cortex and Medulla are both crisscrossed by a a network of stromal cellsnetwork of stromal cells composed of composed of

bull loosely packed thymic epithelial cells loosely packed thymic epithelial cells bull interdigitating dendritic cells interdigitating dendritic cells bull macrophages macrophages

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 5: Functional organization of the Immune System

Characteristics of the immune Characteristics of the immune responseresponse

11 SpecificitySpecificity the ability to distinguish the ability to distinguish between antigens between antigens

22 AdaptivenessAdaptiveness the ability to respond to the ability to respond to previously unseen moleculespreviously unseen molecules

33 Recognition of self and non-self Recognition of self and non-self the ability the ability to recognize and respond to molecules that to recognize and respond to molecules that are foreign or lsquonon-self lsquoand the molecules are foreign or lsquonon-self lsquoand the molecules that are lsquoselfrsquothat are lsquoselfrsquo

44 MemoryMemory the ability to recall previous the ability to recall previous contact with a foreign molecule and respond contact with a foreign molecule and respond to it in a learned mannerto it in a learned manner

Functions of immune Functions of immune systemsystem

bull The immune system like any organization The immune system like any organization has members that perform different has members that perform different functions to accomplish a common goalfunctions to accomplish a common goal

11 Provides defenses against pathogensProvides defenses against pathogens

22 Removes dead or worn out cells like RBCsRemoves dead or worn out cells like RBCs

33 Identifies and destroys abnormal cancer Identifies and destroys abnormal cancer cellscells

44 Protects from autoimmune diseasesProtects from autoimmune diseases

55 Rejects tissues cells of foreign antigens Rejects tissues cells of foreign antigens

Main features of Immune Main features of Immune system system

Pattern recognitionPattern recognition

(anomaly detection noise (anomaly detection noise tolerance) tolerance)

distributed No central point of distributed No central point of controlcontrol

diversity diversity

learning learning

memory memory

redundancy redundancy

robustness robustness

feature extraction feature extraction

multilayered andmultilayered and

adaptiveadaptive

Mechanism of immune Mechanism of immune responseresponse

bull The immune system specifically recognizes and The immune system specifically recognizes and selectively eliminates pathogensselectively eliminates pathogens

bull There are two critical steps in the immune There are two critical steps in the immune responseresponse11 Detection eventsDetection events22 Elimination eventsElimination events

bull The detection and elimination of pathogens The detection and elimination of pathogens depend upon the chemical bonding between depend upon the chemical bonding between receptors on the surface of an immune cell and receptors on the surface of an immune cell and epitopes found on the surface of a pathogenepitopes found on the surface of a pathogen

bull The The complementary receptor ndash epitope bindingcomplementary receptor ndash epitope binding ( monospecificity) activates a complex system ( monospecificity) activates a complex system of signalling that mediates the immune responseof signalling that mediates the immune response

Mechanism of immune Mechanism of immune responseresponse

bull Immune Immune recognition phaserecognition phase is critical in is critical in the normal functioning of the systemthe normal functioning of the system

bull This is accomplished by three sets of This is accomplished by three sets of antigen binding molecules antigen binding molecules

11 T- cell antigen receptors (TCR)T- cell antigen receptors (TCR)22 Class I and class II molecules of the Class I and class II molecules of the

MHCMHC33 B-cell antigen receptor (BCR B-cell antigen receptor (BCR

immunoglobulin)immunoglobulin)bull The The effector phaseeffector phase is mediated by a is mediated by a

variety of cells and soluble factorsvariety of cells and soluble factors

Immune SystemImmune System

Two types of immune Two types of immune systemsystem

1048698 1048698 Innate Innate immune systemimmune system

1048698 1048698 Adaptive Adaptive immune systemimmune system

Main Types of Immunity in Main Types of Immunity in ManMan

Immunity

Innate immunity

Adaptive immunity

Natural Artificial

Passive (maternal)

Active (Infection)

Passive (Serotherapy)

Active (Vaccination)

Innate ImmunityInnate Immunitybull responds immediatelyresponds immediatelybull protects the body from all foreign substancesprotects the body from all foreign substancesbull functions on two levelsfunctions on two levelsbull first line of defense ndash prevents entry of first line of defense ndash prevents entry of

pathogenspathogensbull mechanical barriersmechanical barriers

skin mucosa and secretionsskin mucosa and secretionsbull second line of defense ndash inhibits spread of second line of defense ndash inhibits spread of

pathogenpathogenbull antimicrobial proteinsantimicrobial proteinsbull phagocytes and other cellsphagocytes and other cellsbull inflammationinflammation

Three Lines of DefenseThree Lines of Defense

1st Line ndash barriers at portals of entry1st Line ndash barriers at portals of entry10486981048698primarily inborn and nonspecificprimarily inborn and nonspecific

2nd Line ndash protective cells and chemicals2nd Line ndash protective cells and chemicals10486981048698come into play when barriers are breachedcome into play when barriers are breached10486981048698primarily inborn and nonspecificprimarily inborn and nonspecific

3rd Line ndash antibodies and cytotoxic cells3rd Line ndash antibodies and cytotoxic cells10486981048698provides long-term immunity after provides long-term immunity after encountersencounters10486981048698primarily acquired and specificprimarily acquired and specific

Lines of defenseLines of defensebull 11stst lines of defense lines of defense are the physical barriers which include are the physical barriers which include

the skin urine tears ciliary elevator mucosal membrane etcthe skin urine tears ciliary elevator mucosal membrane etc

bull 22ndnd lines of defense lines of defense are the macrophage system are the macrophage system complement fever interferon and inflammation complement fever interferon and inflammation

bull 33rdrd lines of defense lines of defense aare the specific system also known re the specific system also known as acquired or adaptive immunity The specific system consists of B cells (humoral) and T cells (cell-mediated)

Physical and Chemical Physical and Chemical DefensesDefenses

First line of defense-1First line of defense-1

bull The first line of defense are The first line of defense are barrier barrier tissuestissues such as the skin that stop the such as the skin that stop the entry of pathogens into our bodiesentry of pathogens into our bodies

bull If these barrier layers are If these barrier layers are penetrated cells like penetrated cells like macrophages macrophages and neutrophilsand neutrophils engulf foreign engulf foreign organisms and kill them without the organisms and kill them without the need for antibodies need for antibodies

First Line of Defense-2First Line of Defense-2

bull SkinSkin provides an almost impenetrable provides an almost impenetrable biological barrier biological barrier

bull Lysozyme Lysozyme is an enzyme found in tears is an enzyme found in tears and saliva that and saliva that can break down foreign can break down foreign agents agents

bull The clotting of blood near open wounds The clotting of blood near open wounds prevents an open space for antigensprevents an open space for antigens

bull Mucus and cilia found in the nose and Mucus and cilia found in the nose and throat can catch foreign agents then throat can catch foreign agents then sweep them outside via sweep them outside via coughing coughing sneezing and vomiting sneezing and vomiting

bull The cell wall of plants consists of The cell wall of plants consists of fibrous fibrous proteinsproteins which provide a barrier to which provide a barrier to potential parasites (antigens) potential parasites (antigens)

A second line of defense-1A second line of defense-1

bull A second line of defense is the specific or A second line of defense is the specific or adaptive adaptive immune systemimmune system which may take days to respond which may take days to respond to a primary invasion to a primary invasion

bull The The production of antibodies and cell-mediated production of antibodies and cell-mediated responsesresponses may occur in which specific cells may occur in which specific cells recognize foreign pathogens and destroy themrecognize foreign pathogens and destroy them

bull The response is often more rapid because of the The response is often more rapid because of the activation of memory B and T cellsactivation of memory B and T cells

bull cells of the immune system interact with one cells of the immune system interact with one another by a variety of another by a variety of signal moleculessignal molecules

bull These signals may be proteins such as These signals may be proteins such as lymphokines cytokines and chemokineslymphokines cytokines and chemokines which which stimulate cells of the immune system stimulate cells of the immune system

Second Line of Defense-2Second Line of Defense-2

bull Second lines of defense deal with Second lines of defense deal with antigens that have bypassed the first antigens that have bypassed the first lines of defense lines of defense

bull InterferonsInterferons are a family of proteins that are a family of proteins that are released by a cell that is under are released by a cell that is under attack by an antigen attack by an antigen

bull One method of attacking antigens is by One method of attacking antigens is by phagocytosisphagocytosis where the contents of where the contents of the antigen are broken down by the antigen are broken down by molecules called phagocytesmolecules called phagocytes

Adaptive immunityAdaptive immunity

bull The The second levelsecond level of defence increases in of defence increases in strength and effectiveness with each strength and effectiveness with each encounter The foreign agent is recognised encounter The foreign agent is recognised in a specific manner and the immune system in a specific manner and the immune system acquires memory towards it acquires memory towards it

bull The first encounter with an antigen is The first encounter with an antigen is known as known as the primary responsethe primary response Re- Re-encounter with the same antigen causes a encounter with the same antigen causes a secondary responsesecondary response that is more rapid and that is more rapid and powerfulpowerful

Adaptive immunityAdaptive immunitybull As response produce antibodies to specific As response produce antibodies to specific

infectionsinfections

Some featuresSome features

ndash ndash MemoryMemorybull Each successive encounter with the same Each successive encounter with the same

pathogen improve the responsepathogen improve the response

ndash ndash Clonal selectionClonal selectionbull Select the best and matured immune cells Select the best and matured immune cells

to defend the organism against infectionsto defend the organism against infections

bull Whenever T cells and B cells are activated Whenever T cells and B cells are activated some become some become memory cellsmemory cells The next time The next time that an individual encounters that same that an individual encounters that same antigen the immune system is primed to antigen the immune system is primed to destroy it quickly This is destroy it quickly This is active immunityactive immunity

bull Long-term active immunityLong-term active immunity can be naturally can be naturally acquired by infection or artificially acquired acquired by infection or artificially acquired by vaccines by vaccines

bull Short-term passive immunityShort-term passive immunity can be can be transferred artificially from one individual to transferred artificially from one individual to another via antibody-rich serum another via antibody-rich serum

Active and Passive Acquired Active and Passive Acquired ImmunityImmunity

bull Active immunityActive immunity

ndash Conferred by recovery from infectious diseaseConferred by recovery from infectious disease

ndash Depends on persons own immune systemDepends on persons own immune system

ndash May be acquired artificially with May be acquired artificially with vaccinesvaccines

bull Passive immunityPassive immunity

ndash transferred from person to person through transfer of antibodiestransferred from person to person through transfer of antibodies

ndash Natural instances include antibodies passing across placenta from Natural instances include antibodies passing across placenta from mother to fetus (provides temporary protection) or through the mother to fetus (provides temporary protection) or through the milkmilk

ndash Transferred artificially Eg antibody injections for rabies anti Transferred artificially Eg antibody injections for rabies anti rhesus factor snake venom botulinun toxinrhesus factor snake venom botulinun toxin

bull Lymphatic vessels are responsible for flow of lymph Lymphatic vessels are responsible for flow of lymph within the lymphoid system within the lymphoid system

bull Plasma constantly leaks out of capillaries to deliver Plasma constantly leaks out of capillaries to deliver oxygen and nutrients to cells of the surrounding oxygen and nutrients to cells of the surrounding tissue Once in the tissue the plasma is now called tissue Once in the tissue the plasma is now called tissue fluidtissue fluid

bull While most of this tissue fluid re-enters capillaries While most of this tissue fluid re-enters capillaries and is returned directly to the bloodstream some and is returned directly to the bloodstream some fluid enters lymph vessels as fluid enters lymph vessels as lymph lymph

bull LYMPH-LYMPH- flows from the intercellular tissue spaces flows from the intercellular tissue spaces into lymphatic capillaries and then into a series of into lymphatic capillaries and then into a series of larger collecting vessels called larger collecting vessels called lymphatic vesselslymphatic vessels Lymphatic vessels converge into Lymphatic vessels converge into the thoracic ductthe thoracic duct which returns the fluid to the circulatory system by which returns the fluid to the circulatory system by dumping into the left dumping into the left subclavian vein subclavian vein

Thoracicduct

Overview of blood and lymph system and how Overview of blood and lymph system and how leukocytes travel from one system to anotherleukocytes travel from one system to another

Site of exchange between theblood and lymph systems

Lymph carrying antibodiesand immune cells collect in thoracic duct where the lymph empties back into the blood circulatory system

Immune cells travel back and forth from Immune cells travel back and forth from the blood and lymph circulatory systems the blood and lymph circulatory systems and interact with extra-vascular tissues and interact with extra-vascular tissues

in the process--in the process--extravasationextravasation

muscle

Lymphatic vessels Lymphatic vessels

The organs of the The organs of the immune system immune system

Kinds of lymphoid Kinds of lymphoid OrgansOrgans

Primarycentral lymphoid organsPrimarycentral lymphoid organs ndash bone marrow bone marrow ndash thymus thymus

Secondary peripheral lymphoid tissueSecondary peripheral lymphoid tissuendash lymph nodes lymph nodes ndash spleenspleenndash mucosa-associated lymphoid tissuemucosa-associated lymphoid tissue

Kinds of Lymphoid Organs Kinds of Lymphoid Organs The Lymphoid

Organs

Primary or Central organs

Secondary or Peripheral organs

1Bone marrow2Thymus gland3Bursa of fabricius

1Lymp nodes 2Spleen

3Diffuse lymphoid tissues

bull The The bone marrowbone marrow and the and the thymusthymus constitute constitute the primary lymphoid organsthe primary lymphoid organs

bull Both Both B-lymphocytesB-lymphocytes and and T-lymphocytesT-lymphocytes are are produced from stem cells in the bone produced from stem cells in the bone marrow marrow B-lymphocytes mature in the B-lymphocytes mature in the bone marrow while T-lymphocytes bone marrow while T-lymphocytes migrate to the thymus and mature migrate to the thymus and mature therethere

bull After maturation both B-lymphocytes and T-After maturation both B-lymphocytes and T-lymphocytes circulate through and lymphocytes circulate through and accumulate in accumulate in secondary lymphoid organssecondary lymphoid organs

bull The secondary lymphoid organs include lymph nodes The secondary lymphoid organs include lymph nodes and the spleen as well as lymphoid tissues and the spleen as well as lymphoid tissues

bull The lymphoid tissues include The lymphoid tissues include the tonsils the the tonsils the appendix the Peyers patchesappendix the Peyers patches in the lining of the in the lining of the small intestines (small intestines (gut-associated lymphoid tissue or gut-associated lymphoid tissue or GALTGALT) )

bull The lymphoid tissue found beneath the mucous The lymphoid tissue found beneath the mucous membranes of the bronchi (membranes of the bronchi (bronchial-associated bronchial-associated lymphoid tissue or BALTlymphoid tissue or BALT) )

bull The lymphatic tissue found in the mucous The lymphatic tissue found in the mucous membranes (membranes (mucosa-associated lymphoid tissue or mucosa-associated lymphoid tissue or MALTMALT))

bull The lymphatic tissue found beneath the skin (The lymphatic tissue found beneath the skin (skin-skin-associated lymphoid tissue or SALTassociated lymphoid tissue or SALT) )

Primary and SecondaryPrimary and Secondary Lymphoid organs Lymphoid organs

Primarycentral lymphoid Primarycentral lymphoid organs organs

BONE MARROWBONE MARROW is a central organ is a central organ where all the immune cells are where all the immune cells are born and only B cells mature born and only B cells mature (process termed as (process termed as B B lymphopoiesis) lymphopoiesis)

THYMUSTHYMUS is the other central organ is the other central organ in which T cells mature (in which T cells mature (T T lymphopoiesislymphopoiesis) )

The bone marrowThe bone marrow

Bone marrow is a spongy tissue found Bone marrow is a spongy tissue found within boneswithin bonesAll blood cells are produced within the bone All blood cells are produced within the bone marrowmarrowThe bone marrow of an adult produce about The bone marrow of an adult produce about three million red blood cells and 120000 three million red blood cells and 120000 white blood cells every second white blood cells every second All these cells originate from a small All these cells originate from a small population of stem cells which may be as population of stem cells which may be as few as one in a million of the bone marrow few as one in a million of the bone marrow cells cells

ThymuThymuss

bullThe thymus is an organ located in the The thymus is an organ located in the upper chestupper chest bullImmature lymphocytes leave the bone Immature lymphocytes leave the bone marrow and find their way to the thymus marrow and find their way to the thymus where they are ldquoeducatedrdquo to become where they are ldquoeducatedrdquo to become mature T-lymphocytesmature T-lymphocytes

ThymusThymusFlat bilobed organ situated above the heart Flat bilobed organ situated above the heart

and below the thyroid glandand below the thyroid gland Each lobe is surrounded by a capsule and is Each lobe is surrounded by a capsule and is

divided into lobules divided into lobules The lobules are separated from each other by The lobules are separated from each other by

strands of connective tissue called strands of connective tissue called trabeculaetrabeculae

Each lobule is organized into two Each lobule is organized into two compartments the compartments the cortex cortex (outer (outer compartment) the compartment) the medullamedulla (inner (inner compartment) compartment)

bull Cortex and Medulla are both crisscrossed by Cortex and Medulla are both crisscrossed by a a network of stromal cellsnetwork of stromal cells composed of composed of

bull loosely packed thymic epithelial cells loosely packed thymic epithelial cells bull interdigitating dendritic cells interdigitating dendritic cells bull macrophages macrophages

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 6: Functional organization of the Immune System

Functions of immune Functions of immune systemsystem

bull The immune system like any organization The immune system like any organization has members that perform different has members that perform different functions to accomplish a common goalfunctions to accomplish a common goal

11 Provides defenses against pathogensProvides defenses against pathogens

22 Removes dead or worn out cells like RBCsRemoves dead or worn out cells like RBCs

33 Identifies and destroys abnormal cancer Identifies and destroys abnormal cancer cellscells

44 Protects from autoimmune diseasesProtects from autoimmune diseases

55 Rejects tissues cells of foreign antigens Rejects tissues cells of foreign antigens

Main features of Immune Main features of Immune system system

Pattern recognitionPattern recognition

(anomaly detection noise (anomaly detection noise tolerance) tolerance)

distributed No central point of distributed No central point of controlcontrol

diversity diversity

learning learning

memory memory

redundancy redundancy

robustness robustness

feature extraction feature extraction

multilayered andmultilayered and

adaptiveadaptive

Mechanism of immune Mechanism of immune responseresponse

bull The immune system specifically recognizes and The immune system specifically recognizes and selectively eliminates pathogensselectively eliminates pathogens

bull There are two critical steps in the immune There are two critical steps in the immune responseresponse11 Detection eventsDetection events22 Elimination eventsElimination events

bull The detection and elimination of pathogens The detection and elimination of pathogens depend upon the chemical bonding between depend upon the chemical bonding between receptors on the surface of an immune cell and receptors on the surface of an immune cell and epitopes found on the surface of a pathogenepitopes found on the surface of a pathogen

bull The The complementary receptor ndash epitope bindingcomplementary receptor ndash epitope binding ( monospecificity) activates a complex system ( monospecificity) activates a complex system of signalling that mediates the immune responseof signalling that mediates the immune response

Mechanism of immune Mechanism of immune responseresponse

bull Immune Immune recognition phaserecognition phase is critical in is critical in the normal functioning of the systemthe normal functioning of the system

bull This is accomplished by three sets of This is accomplished by three sets of antigen binding molecules antigen binding molecules

11 T- cell antigen receptors (TCR)T- cell antigen receptors (TCR)22 Class I and class II molecules of the Class I and class II molecules of the

MHCMHC33 B-cell antigen receptor (BCR B-cell antigen receptor (BCR

immunoglobulin)immunoglobulin)bull The The effector phaseeffector phase is mediated by a is mediated by a

variety of cells and soluble factorsvariety of cells and soluble factors

Immune SystemImmune System

Two types of immune Two types of immune systemsystem

1048698 1048698 Innate Innate immune systemimmune system

1048698 1048698 Adaptive Adaptive immune systemimmune system

Main Types of Immunity in Main Types of Immunity in ManMan

Immunity

Innate immunity

Adaptive immunity

Natural Artificial

Passive (maternal)

Active (Infection)

Passive (Serotherapy)

Active (Vaccination)

Innate ImmunityInnate Immunitybull responds immediatelyresponds immediatelybull protects the body from all foreign substancesprotects the body from all foreign substancesbull functions on two levelsfunctions on two levelsbull first line of defense ndash prevents entry of first line of defense ndash prevents entry of

pathogenspathogensbull mechanical barriersmechanical barriers

skin mucosa and secretionsskin mucosa and secretionsbull second line of defense ndash inhibits spread of second line of defense ndash inhibits spread of

pathogenpathogenbull antimicrobial proteinsantimicrobial proteinsbull phagocytes and other cellsphagocytes and other cellsbull inflammationinflammation

Three Lines of DefenseThree Lines of Defense

1st Line ndash barriers at portals of entry1st Line ndash barriers at portals of entry10486981048698primarily inborn and nonspecificprimarily inborn and nonspecific

2nd Line ndash protective cells and chemicals2nd Line ndash protective cells and chemicals10486981048698come into play when barriers are breachedcome into play when barriers are breached10486981048698primarily inborn and nonspecificprimarily inborn and nonspecific

3rd Line ndash antibodies and cytotoxic cells3rd Line ndash antibodies and cytotoxic cells10486981048698provides long-term immunity after provides long-term immunity after encountersencounters10486981048698primarily acquired and specificprimarily acquired and specific

Lines of defenseLines of defensebull 11stst lines of defense lines of defense are the physical barriers which include are the physical barriers which include

the skin urine tears ciliary elevator mucosal membrane etcthe skin urine tears ciliary elevator mucosal membrane etc

bull 22ndnd lines of defense lines of defense are the macrophage system are the macrophage system complement fever interferon and inflammation complement fever interferon and inflammation

bull 33rdrd lines of defense lines of defense aare the specific system also known re the specific system also known as acquired or adaptive immunity The specific system consists of B cells (humoral) and T cells (cell-mediated)

Physical and Chemical Physical and Chemical DefensesDefenses

First line of defense-1First line of defense-1

bull The first line of defense are The first line of defense are barrier barrier tissuestissues such as the skin that stop the such as the skin that stop the entry of pathogens into our bodiesentry of pathogens into our bodies

bull If these barrier layers are If these barrier layers are penetrated cells like penetrated cells like macrophages macrophages and neutrophilsand neutrophils engulf foreign engulf foreign organisms and kill them without the organisms and kill them without the need for antibodies need for antibodies

First Line of Defense-2First Line of Defense-2

bull SkinSkin provides an almost impenetrable provides an almost impenetrable biological barrier biological barrier

bull Lysozyme Lysozyme is an enzyme found in tears is an enzyme found in tears and saliva that and saliva that can break down foreign can break down foreign agents agents

bull The clotting of blood near open wounds The clotting of blood near open wounds prevents an open space for antigensprevents an open space for antigens

bull Mucus and cilia found in the nose and Mucus and cilia found in the nose and throat can catch foreign agents then throat can catch foreign agents then sweep them outside via sweep them outside via coughing coughing sneezing and vomiting sneezing and vomiting

bull The cell wall of plants consists of The cell wall of plants consists of fibrous fibrous proteinsproteins which provide a barrier to which provide a barrier to potential parasites (antigens) potential parasites (antigens)

A second line of defense-1A second line of defense-1

bull A second line of defense is the specific or A second line of defense is the specific or adaptive adaptive immune systemimmune system which may take days to respond which may take days to respond to a primary invasion to a primary invasion

bull The The production of antibodies and cell-mediated production of antibodies and cell-mediated responsesresponses may occur in which specific cells may occur in which specific cells recognize foreign pathogens and destroy themrecognize foreign pathogens and destroy them

bull The response is often more rapid because of the The response is often more rapid because of the activation of memory B and T cellsactivation of memory B and T cells

bull cells of the immune system interact with one cells of the immune system interact with one another by a variety of another by a variety of signal moleculessignal molecules

bull These signals may be proteins such as These signals may be proteins such as lymphokines cytokines and chemokineslymphokines cytokines and chemokines which which stimulate cells of the immune system stimulate cells of the immune system

Second Line of Defense-2Second Line of Defense-2

bull Second lines of defense deal with Second lines of defense deal with antigens that have bypassed the first antigens that have bypassed the first lines of defense lines of defense

bull InterferonsInterferons are a family of proteins that are a family of proteins that are released by a cell that is under are released by a cell that is under attack by an antigen attack by an antigen

bull One method of attacking antigens is by One method of attacking antigens is by phagocytosisphagocytosis where the contents of where the contents of the antigen are broken down by the antigen are broken down by molecules called phagocytesmolecules called phagocytes

Adaptive immunityAdaptive immunity

bull The The second levelsecond level of defence increases in of defence increases in strength and effectiveness with each strength and effectiveness with each encounter The foreign agent is recognised encounter The foreign agent is recognised in a specific manner and the immune system in a specific manner and the immune system acquires memory towards it acquires memory towards it

bull The first encounter with an antigen is The first encounter with an antigen is known as known as the primary responsethe primary response Re- Re-encounter with the same antigen causes a encounter with the same antigen causes a secondary responsesecondary response that is more rapid and that is more rapid and powerfulpowerful

Adaptive immunityAdaptive immunitybull As response produce antibodies to specific As response produce antibodies to specific

infectionsinfections

Some featuresSome features

ndash ndash MemoryMemorybull Each successive encounter with the same Each successive encounter with the same

pathogen improve the responsepathogen improve the response

ndash ndash Clonal selectionClonal selectionbull Select the best and matured immune cells Select the best and matured immune cells

to defend the organism against infectionsto defend the organism against infections

bull Whenever T cells and B cells are activated Whenever T cells and B cells are activated some become some become memory cellsmemory cells The next time The next time that an individual encounters that same that an individual encounters that same antigen the immune system is primed to antigen the immune system is primed to destroy it quickly This is destroy it quickly This is active immunityactive immunity

bull Long-term active immunityLong-term active immunity can be naturally can be naturally acquired by infection or artificially acquired acquired by infection or artificially acquired by vaccines by vaccines

bull Short-term passive immunityShort-term passive immunity can be can be transferred artificially from one individual to transferred artificially from one individual to another via antibody-rich serum another via antibody-rich serum

Active and Passive Acquired Active and Passive Acquired ImmunityImmunity

bull Active immunityActive immunity

ndash Conferred by recovery from infectious diseaseConferred by recovery from infectious disease

ndash Depends on persons own immune systemDepends on persons own immune system

ndash May be acquired artificially with May be acquired artificially with vaccinesvaccines

bull Passive immunityPassive immunity

ndash transferred from person to person through transfer of antibodiestransferred from person to person through transfer of antibodies

ndash Natural instances include antibodies passing across placenta from Natural instances include antibodies passing across placenta from mother to fetus (provides temporary protection) or through the mother to fetus (provides temporary protection) or through the milkmilk

ndash Transferred artificially Eg antibody injections for rabies anti Transferred artificially Eg antibody injections for rabies anti rhesus factor snake venom botulinun toxinrhesus factor snake venom botulinun toxin

bull Lymphatic vessels are responsible for flow of lymph Lymphatic vessels are responsible for flow of lymph within the lymphoid system within the lymphoid system

bull Plasma constantly leaks out of capillaries to deliver Plasma constantly leaks out of capillaries to deliver oxygen and nutrients to cells of the surrounding oxygen and nutrients to cells of the surrounding tissue Once in the tissue the plasma is now called tissue Once in the tissue the plasma is now called tissue fluidtissue fluid

bull While most of this tissue fluid re-enters capillaries While most of this tissue fluid re-enters capillaries and is returned directly to the bloodstream some and is returned directly to the bloodstream some fluid enters lymph vessels as fluid enters lymph vessels as lymph lymph

bull LYMPH-LYMPH- flows from the intercellular tissue spaces flows from the intercellular tissue spaces into lymphatic capillaries and then into a series of into lymphatic capillaries and then into a series of larger collecting vessels called larger collecting vessels called lymphatic vesselslymphatic vessels Lymphatic vessels converge into Lymphatic vessels converge into the thoracic ductthe thoracic duct which returns the fluid to the circulatory system by which returns the fluid to the circulatory system by dumping into the left dumping into the left subclavian vein subclavian vein

Thoracicduct

Overview of blood and lymph system and how Overview of blood and lymph system and how leukocytes travel from one system to anotherleukocytes travel from one system to another

Site of exchange between theblood and lymph systems

Lymph carrying antibodiesand immune cells collect in thoracic duct where the lymph empties back into the blood circulatory system

Immune cells travel back and forth from Immune cells travel back and forth from the blood and lymph circulatory systems the blood and lymph circulatory systems and interact with extra-vascular tissues and interact with extra-vascular tissues

in the process--in the process--extravasationextravasation

muscle

Lymphatic vessels Lymphatic vessels

The organs of the The organs of the immune system immune system

Kinds of lymphoid Kinds of lymphoid OrgansOrgans

Primarycentral lymphoid organsPrimarycentral lymphoid organs ndash bone marrow bone marrow ndash thymus thymus

Secondary peripheral lymphoid tissueSecondary peripheral lymphoid tissuendash lymph nodes lymph nodes ndash spleenspleenndash mucosa-associated lymphoid tissuemucosa-associated lymphoid tissue

Kinds of Lymphoid Organs Kinds of Lymphoid Organs The Lymphoid

Organs

Primary or Central organs

Secondary or Peripheral organs

1Bone marrow2Thymus gland3Bursa of fabricius

1Lymp nodes 2Spleen

3Diffuse lymphoid tissues

bull The The bone marrowbone marrow and the and the thymusthymus constitute constitute the primary lymphoid organsthe primary lymphoid organs

bull Both Both B-lymphocytesB-lymphocytes and and T-lymphocytesT-lymphocytes are are produced from stem cells in the bone produced from stem cells in the bone marrow marrow B-lymphocytes mature in the B-lymphocytes mature in the bone marrow while T-lymphocytes bone marrow while T-lymphocytes migrate to the thymus and mature migrate to the thymus and mature therethere

bull After maturation both B-lymphocytes and T-After maturation both B-lymphocytes and T-lymphocytes circulate through and lymphocytes circulate through and accumulate in accumulate in secondary lymphoid organssecondary lymphoid organs

bull The secondary lymphoid organs include lymph nodes The secondary lymphoid organs include lymph nodes and the spleen as well as lymphoid tissues and the spleen as well as lymphoid tissues

bull The lymphoid tissues include The lymphoid tissues include the tonsils the the tonsils the appendix the Peyers patchesappendix the Peyers patches in the lining of the in the lining of the small intestines (small intestines (gut-associated lymphoid tissue or gut-associated lymphoid tissue or GALTGALT) )

bull The lymphoid tissue found beneath the mucous The lymphoid tissue found beneath the mucous membranes of the bronchi (membranes of the bronchi (bronchial-associated bronchial-associated lymphoid tissue or BALTlymphoid tissue or BALT) )

bull The lymphatic tissue found in the mucous The lymphatic tissue found in the mucous membranes (membranes (mucosa-associated lymphoid tissue or mucosa-associated lymphoid tissue or MALTMALT))

bull The lymphatic tissue found beneath the skin (The lymphatic tissue found beneath the skin (skin-skin-associated lymphoid tissue or SALTassociated lymphoid tissue or SALT) )

Primary and SecondaryPrimary and Secondary Lymphoid organs Lymphoid organs

Primarycentral lymphoid Primarycentral lymphoid organs organs

BONE MARROWBONE MARROW is a central organ is a central organ where all the immune cells are where all the immune cells are born and only B cells mature born and only B cells mature (process termed as (process termed as B B lymphopoiesis) lymphopoiesis)

THYMUSTHYMUS is the other central organ is the other central organ in which T cells mature (in which T cells mature (T T lymphopoiesislymphopoiesis) )

The bone marrowThe bone marrow

Bone marrow is a spongy tissue found Bone marrow is a spongy tissue found within boneswithin bonesAll blood cells are produced within the bone All blood cells are produced within the bone marrowmarrowThe bone marrow of an adult produce about The bone marrow of an adult produce about three million red blood cells and 120000 three million red blood cells and 120000 white blood cells every second white blood cells every second All these cells originate from a small All these cells originate from a small population of stem cells which may be as population of stem cells which may be as few as one in a million of the bone marrow few as one in a million of the bone marrow cells cells

ThymuThymuss

bullThe thymus is an organ located in the The thymus is an organ located in the upper chestupper chest bullImmature lymphocytes leave the bone Immature lymphocytes leave the bone marrow and find their way to the thymus marrow and find their way to the thymus where they are ldquoeducatedrdquo to become where they are ldquoeducatedrdquo to become mature T-lymphocytesmature T-lymphocytes

ThymusThymusFlat bilobed organ situated above the heart Flat bilobed organ situated above the heart

and below the thyroid glandand below the thyroid gland Each lobe is surrounded by a capsule and is Each lobe is surrounded by a capsule and is

divided into lobules divided into lobules The lobules are separated from each other by The lobules are separated from each other by

strands of connective tissue called strands of connective tissue called trabeculaetrabeculae

Each lobule is organized into two Each lobule is organized into two compartments the compartments the cortex cortex (outer (outer compartment) the compartment) the medullamedulla (inner (inner compartment) compartment)

bull Cortex and Medulla are both crisscrossed by Cortex and Medulla are both crisscrossed by a a network of stromal cellsnetwork of stromal cells composed of composed of

bull loosely packed thymic epithelial cells loosely packed thymic epithelial cells bull interdigitating dendritic cells interdigitating dendritic cells bull macrophages macrophages

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 7: Functional organization of the Immune System

Main features of Immune Main features of Immune system system

Pattern recognitionPattern recognition

(anomaly detection noise (anomaly detection noise tolerance) tolerance)

distributed No central point of distributed No central point of controlcontrol

diversity diversity

learning learning

memory memory

redundancy redundancy

robustness robustness

feature extraction feature extraction

multilayered andmultilayered and

adaptiveadaptive

Mechanism of immune Mechanism of immune responseresponse

bull The immune system specifically recognizes and The immune system specifically recognizes and selectively eliminates pathogensselectively eliminates pathogens

bull There are two critical steps in the immune There are two critical steps in the immune responseresponse11 Detection eventsDetection events22 Elimination eventsElimination events

bull The detection and elimination of pathogens The detection and elimination of pathogens depend upon the chemical bonding between depend upon the chemical bonding between receptors on the surface of an immune cell and receptors on the surface of an immune cell and epitopes found on the surface of a pathogenepitopes found on the surface of a pathogen

bull The The complementary receptor ndash epitope bindingcomplementary receptor ndash epitope binding ( monospecificity) activates a complex system ( monospecificity) activates a complex system of signalling that mediates the immune responseof signalling that mediates the immune response

Mechanism of immune Mechanism of immune responseresponse

bull Immune Immune recognition phaserecognition phase is critical in is critical in the normal functioning of the systemthe normal functioning of the system

bull This is accomplished by three sets of This is accomplished by three sets of antigen binding molecules antigen binding molecules

11 T- cell antigen receptors (TCR)T- cell antigen receptors (TCR)22 Class I and class II molecules of the Class I and class II molecules of the

MHCMHC33 B-cell antigen receptor (BCR B-cell antigen receptor (BCR

immunoglobulin)immunoglobulin)bull The The effector phaseeffector phase is mediated by a is mediated by a

variety of cells and soluble factorsvariety of cells and soluble factors

Immune SystemImmune System

Two types of immune Two types of immune systemsystem

1048698 1048698 Innate Innate immune systemimmune system

1048698 1048698 Adaptive Adaptive immune systemimmune system

Main Types of Immunity in Main Types of Immunity in ManMan

Immunity

Innate immunity

Adaptive immunity

Natural Artificial

Passive (maternal)

Active (Infection)

Passive (Serotherapy)

Active (Vaccination)

Innate ImmunityInnate Immunitybull responds immediatelyresponds immediatelybull protects the body from all foreign substancesprotects the body from all foreign substancesbull functions on two levelsfunctions on two levelsbull first line of defense ndash prevents entry of first line of defense ndash prevents entry of

pathogenspathogensbull mechanical barriersmechanical barriers

skin mucosa and secretionsskin mucosa and secretionsbull second line of defense ndash inhibits spread of second line of defense ndash inhibits spread of

pathogenpathogenbull antimicrobial proteinsantimicrobial proteinsbull phagocytes and other cellsphagocytes and other cellsbull inflammationinflammation

Three Lines of DefenseThree Lines of Defense

1st Line ndash barriers at portals of entry1st Line ndash barriers at portals of entry10486981048698primarily inborn and nonspecificprimarily inborn and nonspecific

2nd Line ndash protective cells and chemicals2nd Line ndash protective cells and chemicals10486981048698come into play when barriers are breachedcome into play when barriers are breached10486981048698primarily inborn and nonspecificprimarily inborn and nonspecific

3rd Line ndash antibodies and cytotoxic cells3rd Line ndash antibodies and cytotoxic cells10486981048698provides long-term immunity after provides long-term immunity after encountersencounters10486981048698primarily acquired and specificprimarily acquired and specific

Lines of defenseLines of defensebull 11stst lines of defense lines of defense are the physical barriers which include are the physical barriers which include

the skin urine tears ciliary elevator mucosal membrane etcthe skin urine tears ciliary elevator mucosal membrane etc

bull 22ndnd lines of defense lines of defense are the macrophage system are the macrophage system complement fever interferon and inflammation complement fever interferon and inflammation

bull 33rdrd lines of defense lines of defense aare the specific system also known re the specific system also known as acquired or adaptive immunity The specific system consists of B cells (humoral) and T cells (cell-mediated)

Physical and Chemical Physical and Chemical DefensesDefenses

First line of defense-1First line of defense-1

bull The first line of defense are The first line of defense are barrier barrier tissuestissues such as the skin that stop the such as the skin that stop the entry of pathogens into our bodiesentry of pathogens into our bodies

bull If these barrier layers are If these barrier layers are penetrated cells like penetrated cells like macrophages macrophages and neutrophilsand neutrophils engulf foreign engulf foreign organisms and kill them without the organisms and kill them without the need for antibodies need for antibodies

First Line of Defense-2First Line of Defense-2

bull SkinSkin provides an almost impenetrable provides an almost impenetrable biological barrier biological barrier

bull Lysozyme Lysozyme is an enzyme found in tears is an enzyme found in tears and saliva that and saliva that can break down foreign can break down foreign agents agents

bull The clotting of blood near open wounds The clotting of blood near open wounds prevents an open space for antigensprevents an open space for antigens

bull Mucus and cilia found in the nose and Mucus and cilia found in the nose and throat can catch foreign agents then throat can catch foreign agents then sweep them outside via sweep them outside via coughing coughing sneezing and vomiting sneezing and vomiting

bull The cell wall of plants consists of The cell wall of plants consists of fibrous fibrous proteinsproteins which provide a barrier to which provide a barrier to potential parasites (antigens) potential parasites (antigens)

A second line of defense-1A second line of defense-1

bull A second line of defense is the specific or A second line of defense is the specific or adaptive adaptive immune systemimmune system which may take days to respond which may take days to respond to a primary invasion to a primary invasion

bull The The production of antibodies and cell-mediated production of antibodies and cell-mediated responsesresponses may occur in which specific cells may occur in which specific cells recognize foreign pathogens and destroy themrecognize foreign pathogens and destroy them

bull The response is often more rapid because of the The response is often more rapid because of the activation of memory B and T cellsactivation of memory B and T cells

bull cells of the immune system interact with one cells of the immune system interact with one another by a variety of another by a variety of signal moleculessignal molecules

bull These signals may be proteins such as These signals may be proteins such as lymphokines cytokines and chemokineslymphokines cytokines and chemokines which which stimulate cells of the immune system stimulate cells of the immune system

Second Line of Defense-2Second Line of Defense-2

bull Second lines of defense deal with Second lines of defense deal with antigens that have bypassed the first antigens that have bypassed the first lines of defense lines of defense

bull InterferonsInterferons are a family of proteins that are a family of proteins that are released by a cell that is under are released by a cell that is under attack by an antigen attack by an antigen

bull One method of attacking antigens is by One method of attacking antigens is by phagocytosisphagocytosis where the contents of where the contents of the antigen are broken down by the antigen are broken down by molecules called phagocytesmolecules called phagocytes

Adaptive immunityAdaptive immunity

bull The The second levelsecond level of defence increases in of defence increases in strength and effectiveness with each strength and effectiveness with each encounter The foreign agent is recognised encounter The foreign agent is recognised in a specific manner and the immune system in a specific manner and the immune system acquires memory towards it acquires memory towards it

bull The first encounter with an antigen is The first encounter with an antigen is known as known as the primary responsethe primary response Re- Re-encounter with the same antigen causes a encounter with the same antigen causes a secondary responsesecondary response that is more rapid and that is more rapid and powerfulpowerful

Adaptive immunityAdaptive immunitybull As response produce antibodies to specific As response produce antibodies to specific

infectionsinfections

Some featuresSome features

ndash ndash MemoryMemorybull Each successive encounter with the same Each successive encounter with the same

pathogen improve the responsepathogen improve the response

ndash ndash Clonal selectionClonal selectionbull Select the best and matured immune cells Select the best and matured immune cells

to defend the organism against infectionsto defend the organism against infections

bull Whenever T cells and B cells are activated Whenever T cells and B cells are activated some become some become memory cellsmemory cells The next time The next time that an individual encounters that same that an individual encounters that same antigen the immune system is primed to antigen the immune system is primed to destroy it quickly This is destroy it quickly This is active immunityactive immunity

bull Long-term active immunityLong-term active immunity can be naturally can be naturally acquired by infection or artificially acquired acquired by infection or artificially acquired by vaccines by vaccines

bull Short-term passive immunityShort-term passive immunity can be can be transferred artificially from one individual to transferred artificially from one individual to another via antibody-rich serum another via antibody-rich serum

Active and Passive Acquired Active and Passive Acquired ImmunityImmunity

bull Active immunityActive immunity

ndash Conferred by recovery from infectious diseaseConferred by recovery from infectious disease

ndash Depends on persons own immune systemDepends on persons own immune system

ndash May be acquired artificially with May be acquired artificially with vaccinesvaccines

bull Passive immunityPassive immunity

ndash transferred from person to person through transfer of antibodiestransferred from person to person through transfer of antibodies

ndash Natural instances include antibodies passing across placenta from Natural instances include antibodies passing across placenta from mother to fetus (provides temporary protection) or through the mother to fetus (provides temporary protection) or through the milkmilk

ndash Transferred artificially Eg antibody injections for rabies anti Transferred artificially Eg antibody injections for rabies anti rhesus factor snake venom botulinun toxinrhesus factor snake venom botulinun toxin

bull Lymphatic vessels are responsible for flow of lymph Lymphatic vessels are responsible for flow of lymph within the lymphoid system within the lymphoid system

bull Plasma constantly leaks out of capillaries to deliver Plasma constantly leaks out of capillaries to deliver oxygen and nutrients to cells of the surrounding oxygen and nutrients to cells of the surrounding tissue Once in the tissue the plasma is now called tissue Once in the tissue the plasma is now called tissue fluidtissue fluid

bull While most of this tissue fluid re-enters capillaries While most of this tissue fluid re-enters capillaries and is returned directly to the bloodstream some and is returned directly to the bloodstream some fluid enters lymph vessels as fluid enters lymph vessels as lymph lymph

bull LYMPH-LYMPH- flows from the intercellular tissue spaces flows from the intercellular tissue spaces into lymphatic capillaries and then into a series of into lymphatic capillaries and then into a series of larger collecting vessels called larger collecting vessels called lymphatic vesselslymphatic vessels Lymphatic vessels converge into Lymphatic vessels converge into the thoracic ductthe thoracic duct which returns the fluid to the circulatory system by which returns the fluid to the circulatory system by dumping into the left dumping into the left subclavian vein subclavian vein

Thoracicduct

Overview of blood and lymph system and how Overview of blood and lymph system and how leukocytes travel from one system to anotherleukocytes travel from one system to another

Site of exchange between theblood and lymph systems

Lymph carrying antibodiesand immune cells collect in thoracic duct where the lymph empties back into the blood circulatory system

Immune cells travel back and forth from Immune cells travel back and forth from the blood and lymph circulatory systems the blood and lymph circulatory systems and interact with extra-vascular tissues and interact with extra-vascular tissues

in the process--in the process--extravasationextravasation

muscle

Lymphatic vessels Lymphatic vessels

The organs of the The organs of the immune system immune system

Kinds of lymphoid Kinds of lymphoid OrgansOrgans

Primarycentral lymphoid organsPrimarycentral lymphoid organs ndash bone marrow bone marrow ndash thymus thymus

Secondary peripheral lymphoid tissueSecondary peripheral lymphoid tissuendash lymph nodes lymph nodes ndash spleenspleenndash mucosa-associated lymphoid tissuemucosa-associated lymphoid tissue

Kinds of Lymphoid Organs Kinds of Lymphoid Organs The Lymphoid

Organs

Primary or Central organs

Secondary or Peripheral organs

1Bone marrow2Thymus gland3Bursa of fabricius

1Lymp nodes 2Spleen

3Diffuse lymphoid tissues

bull The The bone marrowbone marrow and the and the thymusthymus constitute constitute the primary lymphoid organsthe primary lymphoid organs

bull Both Both B-lymphocytesB-lymphocytes and and T-lymphocytesT-lymphocytes are are produced from stem cells in the bone produced from stem cells in the bone marrow marrow B-lymphocytes mature in the B-lymphocytes mature in the bone marrow while T-lymphocytes bone marrow while T-lymphocytes migrate to the thymus and mature migrate to the thymus and mature therethere

bull After maturation both B-lymphocytes and T-After maturation both B-lymphocytes and T-lymphocytes circulate through and lymphocytes circulate through and accumulate in accumulate in secondary lymphoid organssecondary lymphoid organs

bull The secondary lymphoid organs include lymph nodes The secondary lymphoid organs include lymph nodes and the spleen as well as lymphoid tissues and the spleen as well as lymphoid tissues

bull The lymphoid tissues include The lymphoid tissues include the tonsils the the tonsils the appendix the Peyers patchesappendix the Peyers patches in the lining of the in the lining of the small intestines (small intestines (gut-associated lymphoid tissue or gut-associated lymphoid tissue or GALTGALT) )

bull The lymphoid tissue found beneath the mucous The lymphoid tissue found beneath the mucous membranes of the bronchi (membranes of the bronchi (bronchial-associated bronchial-associated lymphoid tissue or BALTlymphoid tissue or BALT) )

bull The lymphatic tissue found in the mucous The lymphatic tissue found in the mucous membranes (membranes (mucosa-associated lymphoid tissue or mucosa-associated lymphoid tissue or MALTMALT))

bull The lymphatic tissue found beneath the skin (The lymphatic tissue found beneath the skin (skin-skin-associated lymphoid tissue or SALTassociated lymphoid tissue or SALT) )

Primary and SecondaryPrimary and Secondary Lymphoid organs Lymphoid organs

Primarycentral lymphoid Primarycentral lymphoid organs organs

BONE MARROWBONE MARROW is a central organ is a central organ where all the immune cells are where all the immune cells are born and only B cells mature born and only B cells mature (process termed as (process termed as B B lymphopoiesis) lymphopoiesis)

THYMUSTHYMUS is the other central organ is the other central organ in which T cells mature (in which T cells mature (T T lymphopoiesislymphopoiesis) )

The bone marrowThe bone marrow

Bone marrow is a spongy tissue found Bone marrow is a spongy tissue found within boneswithin bonesAll blood cells are produced within the bone All blood cells are produced within the bone marrowmarrowThe bone marrow of an adult produce about The bone marrow of an adult produce about three million red blood cells and 120000 three million red blood cells and 120000 white blood cells every second white blood cells every second All these cells originate from a small All these cells originate from a small population of stem cells which may be as population of stem cells which may be as few as one in a million of the bone marrow few as one in a million of the bone marrow cells cells

ThymuThymuss

bullThe thymus is an organ located in the The thymus is an organ located in the upper chestupper chest bullImmature lymphocytes leave the bone Immature lymphocytes leave the bone marrow and find their way to the thymus marrow and find their way to the thymus where they are ldquoeducatedrdquo to become where they are ldquoeducatedrdquo to become mature T-lymphocytesmature T-lymphocytes

ThymusThymusFlat bilobed organ situated above the heart Flat bilobed organ situated above the heart

and below the thyroid glandand below the thyroid gland Each lobe is surrounded by a capsule and is Each lobe is surrounded by a capsule and is

divided into lobules divided into lobules The lobules are separated from each other by The lobules are separated from each other by

strands of connective tissue called strands of connective tissue called trabeculaetrabeculae

Each lobule is organized into two Each lobule is organized into two compartments the compartments the cortex cortex (outer (outer compartment) the compartment) the medullamedulla (inner (inner compartment) compartment)

bull Cortex and Medulla are both crisscrossed by Cortex and Medulla are both crisscrossed by a a network of stromal cellsnetwork of stromal cells composed of composed of

bull loosely packed thymic epithelial cells loosely packed thymic epithelial cells bull interdigitating dendritic cells interdigitating dendritic cells bull macrophages macrophages

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 8: Functional organization of the Immune System

Mechanism of immune Mechanism of immune responseresponse

bull The immune system specifically recognizes and The immune system specifically recognizes and selectively eliminates pathogensselectively eliminates pathogens

bull There are two critical steps in the immune There are two critical steps in the immune responseresponse11 Detection eventsDetection events22 Elimination eventsElimination events

bull The detection and elimination of pathogens The detection and elimination of pathogens depend upon the chemical bonding between depend upon the chemical bonding between receptors on the surface of an immune cell and receptors on the surface of an immune cell and epitopes found on the surface of a pathogenepitopes found on the surface of a pathogen

bull The The complementary receptor ndash epitope bindingcomplementary receptor ndash epitope binding ( monospecificity) activates a complex system ( monospecificity) activates a complex system of signalling that mediates the immune responseof signalling that mediates the immune response

Mechanism of immune Mechanism of immune responseresponse

bull Immune Immune recognition phaserecognition phase is critical in is critical in the normal functioning of the systemthe normal functioning of the system

bull This is accomplished by three sets of This is accomplished by three sets of antigen binding molecules antigen binding molecules

11 T- cell antigen receptors (TCR)T- cell antigen receptors (TCR)22 Class I and class II molecules of the Class I and class II molecules of the

MHCMHC33 B-cell antigen receptor (BCR B-cell antigen receptor (BCR

immunoglobulin)immunoglobulin)bull The The effector phaseeffector phase is mediated by a is mediated by a

variety of cells and soluble factorsvariety of cells and soluble factors

Immune SystemImmune System

Two types of immune Two types of immune systemsystem

1048698 1048698 Innate Innate immune systemimmune system

1048698 1048698 Adaptive Adaptive immune systemimmune system

Main Types of Immunity in Main Types of Immunity in ManMan

Immunity

Innate immunity

Adaptive immunity

Natural Artificial

Passive (maternal)

Active (Infection)

Passive (Serotherapy)

Active (Vaccination)

Innate ImmunityInnate Immunitybull responds immediatelyresponds immediatelybull protects the body from all foreign substancesprotects the body from all foreign substancesbull functions on two levelsfunctions on two levelsbull first line of defense ndash prevents entry of first line of defense ndash prevents entry of

pathogenspathogensbull mechanical barriersmechanical barriers

skin mucosa and secretionsskin mucosa and secretionsbull second line of defense ndash inhibits spread of second line of defense ndash inhibits spread of

pathogenpathogenbull antimicrobial proteinsantimicrobial proteinsbull phagocytes and other cellsphagocytes and other cellsbull inflammationinflammation

Three Lines of DefenseThree Lines of Defense

1st Line ndash barriers at portals of entry1st Line ndash barriers at portals of entry10486981048698primarily inborn and nonspecificprimarily inborn and nonspecific

2nd Line ndash protective cells and chemicals2nd Line ndash protective cells and chemicals10486981048698come into play when barriers are breachedcome into play when barriers are breached10486981048698primarily inborn and nonspecificprimarily inborn and nonspecific

3rd Line ndash antibodies and cytotoxic cells3rd Line ndash antibodies and cytotoxic cells10486981048698provides long-term immunity after provides long-term immunity after encountersencounters10486981048698primarily acquired and specificprimarily acquired and specific

Lines of defenseLines of defensebull 11stst lines of defense lines of defense are the physical barriers which include are the physical barriers which include

the skin urine tears ciliary elevator mucosal membrane etcthe skin urine tears ciliary elevator mucosal membrane etc

bull 22ndnd lines of defense lines of defense are the macrophage system are the macrophage system complement fever interferon and inflammation complement fever interferon and inflammation

bull 33rdrd lines of defense lines of defense aare the specific system also known re the specific system also known as acquired or adaptive immunity The specific system consists of B cells (humoral) and T cells (cell-mediated)

Physical and Chemical Physical and Chemical DefensesDefenses

First line of defense-1First line of defense-1

bull The first line of defense are The first line of defense are barrier barrier tissuestissues such as the skin that stop the such as the skin that stop the entry of pathogens into our bodiesentry of pathogens into our bodies

bull If these barrier layers are If these barrier layers are penetrated cells like penetrated cells like macrophages macrophages and neutrophilsand neutrophils engulf foreign engulf foreign organisms and kill them without the organisms and kill them without the need for antibodies need for antibodies

First Line of Defense-2First Line of Defense-2

bull SkinSkin provides an almost impenetrable provides an almost impenetrable biological barrier biological barrier

bull Lysozyme Lysozyme is an enzyme found in tears is an enzyme found in tears and saliva that and saliva that can break down foreign can break down foreign agents agents

bull The clotting of blood near open wounds The clotting of blood near open wounds prevents an open space for antigensprevents an open space for antigens

bull Mucus and cilia found in the nose and Mucus and cilia found in the nose and throat can catch foreign agents then throat can catch foreign agents then sweep them outside via sweep them outside via coughing coughing sneezing and vomiting sneezing and vomiting

bull The cell wall of plants consists of The cell wall of plants consists of fibrous fibrous proteinsproteins which provide a barrier to which provide a barrier to potential parasites (antigens) potential parasites (antigens)

A second line of defense-1A second line of defense-1

bull A second line of defense is the specific or A second line of defense is the specific or adaptive adaptive immune systemimmune system which may take days to respond which may take days to respond to a primary invasion to a primary invasion

bull The The production of antibodies and cell-mediated production of antibodies and cell-mediated responsesresponses may occur in which specific cells may occur in which specific cells recognize foreign pathogens and destroy themrecognize foreign pathogens and destroy them

bull The response is often more rapid because of the The response is often more rapid because of the activation of memory B and T cellsactivation of memory B and T cells

bull cells of the immune system interact with one cells of the immune system interact with one another by a variety of another by a variety of signal moleculessignal molecules

bull These signals may be proteins such as These signals may be proteins such as lymphokines cytokines and chemokineslymphokines cytokines and chemokines which which stimulate cells of the immune system stimulate cells of the immune system

Second Line of Defense-2Second Line of Defense-2

bull Second lines of defense deal with Second lines of defense deal with antigens that have bypassed the first antigens that have bypassed the first lines of defense lines of defense

bull InterferonsInterferons are a family of proteins that are a family of proteins that are released by a cell that is under are released by a cell that is under attack by an antigen attack by an antigen

bull One method of attacking antigens is by One method of attacking antigens is by phagocytosisphagocytosis where the contents of where the contents of the antigen are broken down by the antigen are broken down by molecules called phagocytesmolecules called phagocytes

Adaptive immunityAdaptive immunity

bull The The second levelsecond level of defence increases in of defence increases in strength and effectiveness with each strength and effectiveness with each encounter The foreign agent is recognised encounter The foreign agent is recognised in a specific manner and the immune system in a specific manner and the immune system acquires memory towards it acquires memory towards it

bull The first encounter with an antigen is The first encounter with an antigen is known as known as the primary responsethe primary response Re- Re-encounter with the same antigen causes a encounter with the same antigen causes a secondary responsesecondary response that is more rapid and that is more rapid and powerfulpowerful

Adaptive immunityAdaptive immunitybull As response produce antibodies to specific As response produce antibodies to specific

infectionsinfections

Some featuresSome features

ndash ndash MemoryMemorybull Each successive encounter with the same Each successive encounter with the same

pathogen improve the responsepathogen improve the response

ndash ndash Clonal selectionClonal selectionbull Select the best and matured immune cells Select the best and matured immune cells

to defend the organism against infectionsto defend the organism against infections

bull Whenever T cells and B cells are activated Whenever T cells and B cells are activated some become some become memory cellsmemory cells The next time The next time that an individual encounters that same that an individual encounters that same antigen the immune system is primed to antigen the immune system is primed to destroy it quickly This is destroy it quickly This is active immunityactive immunity

bull Long-term active immunityLong-term active immunity can be naturally can be naturally acquired by infection or artificially acquired acquired by infection or artificially acquired by vaccines by vaccines

bull Short-term passive immunityShort-term passive immunity can be can be transferred artificially from one individual to transferred artificially from one individual to another via antibody-rich serum another via antibody-rich serum

Active and Passive Acquired Active and Passive Acquired ImmunityImmunity

bull Active immunityActive immunity

ndash Conferred by recovery from infectious diseaseConferred by recovery from infectious disease

ndash Depends on persons own immune systemDepends on persons own immune system

ndash May be acquired artificially with May be acquired artificially with vaccinesvaccines

bull Passive immunityPassive immunity

ndash transferred from person to person through transfer of antibodiestransferred from person to person through transfer of antibodies

ndash Natural instances include antibodies passing across placenta from Natural instances include antibodies passing across placenta from mother to fetus (provides temporary protection) or through the mother to fetus (provides temporary protection) or through the milkmilk

ndash Transferred artificially Eg antibody injections for rabies anti Transferred artificially Eg antibody injections for rabies anti rhesus factor snake venom botulinun toxinrhesus factor snake venom botulinun toxin

bull Lymphatic vessels are responsible for flow of lymph Lymphatic vessels are responsible for flow of lymph within the lymphoid system within the lymphoid system

bull Plasma constantly leaks out of capillaries to deliver Plasma constantly leaks out of capillaries to deliver oxygen and nutrients to cells of the surrounding oxygen and nutrients to cells of the surrounding tissue Once in the tissue the plasma is now called tissue Once in the tissue the plasma is now called tissue fluidtissue fluid

bull While most of this tissue fluid re-enters capillaries While most of this tissue fluid re-enters capillaries and is returned directly to the bloodstream some and is returned directly to the bloodstream some fluid enters lymph vessels as fluid enters lymph vessels as lymph lymph

bull LYMPH-LYMPH- flows from the intercellular tissue spaces flows from the intercellular tissue spaces into lymphatic capillaries and then into a series of into lymphatic capillaries and then into a series of larger collecting vessels called larger collecting vessels called lymphatic vesselslymphatic vessels Lymphatic vessels converge into Lymphatic vessels converge into the thoracic ductthe thoracic duct which returns the fluid to the circulatory system by which returns the fluid to the circulatory system by dumping into the left dumping into the left subclavian vein subclavian vein

Thoracicduct

Overview of blood and lymph system and how Overview of blood and lymph system and how leukocytes travel from one system to anotherleukocytes travel from one system to another

Site of exchange between theblood and lymph systems

Lymph carrying antibodiesand immune cells collect in thoracic duct where the lymph empties back into the blood circulatory system

Immune cells travel back and forth from Immune cells travel back and forth from the blood and lymph circulatory systems the blood and lymph circulatory systems and interact with extra-vascular tissues and interact with extra-vascular tissues

in the process--in the process--extravasationextravasation

muscle

Lymphatic vessels Lymphatic vessels

The organs of the The organs of the immune system immune system

Kinds of lymphoid Kinds of lymphoid OrgansOrgans

Primarycentral lymphoid organsPrimarycentral lymphoid organs ndash bone marrow bone marrow ndash thymus thymus

Secondary peripheral lymphoid tissueSecondary peripheral lymphoid tissuendash lymph nodes lymph nodes ndash spleenspleenndash mucosa-associated lymphoid tissuemucosa-associated lymphoid tissue

Kinds of Lymphoid Organs Kinds of Lymphoid Organs The Lymphoid

Organs

Primary or Central organs

Secondary or Peripheral organs

1Bone marrow2Thymus gland3Bursa of fabricius

1Lymp nodes 2Spleen

3Diffuse lymphoid tissues

bull The The bone marrowbone marrow and the and the thymusthymus constitute constitute the primary lymphoid organsthe primary lymphoid organs

bull Both Both B-lymphocytesB-lymphocytes and and T-lymphocytesT-lymphocytes are are produced from stem cells in the bone produced from stem cells in the bone marrow marrow B-lymphocytes mature in the B-lymphocytes mature in the bone marrow while T-lymphocytes bone marrow while T-lymphocytes migrate to the thymus and mature migrate to the thymus and mature therethere

bull After maturation both B-lymphocytes and T-After maturation both B-lymphocytes and T-lymphocytes circulate through and lymphocytes circulate through and accumulate in accumulate in secondary lymphoid organssecondary lymphoid organs

bull The secondary lymphoid organs include lymph nodes The secondary lymphoid organs include lymph nodes and the spleen as well as lymphoid tissues and the spleen as well as lymphoid tissues

bull The lymphoid tissues include The lymphoid tissues include the tonsils the the tonsils the appendix the Peyers patchesappendix the Peyers patches in the lining of the in the lining of the small intestines (small intestines (gut-associated lymphoid tissue or gut-associated lymphoid tissue or GALTGALT) )

bull The lymphoid tissue found beneath the mucous The lymphoid tissue found beneath the mucous membranes of the bronchi (membranes of the bronchi (bronchial-associated bronchial-associated lymphoid tissue or BALTlymphoid tissue or BALT) )

bull The lymphatic tissue found in the mucous The lymphatic tissue found in the mucous membranes (membranes (mucosa-associated lymphoid tissue or mucosa-associated lymphoid tissue or MALTMALT))

bull The lymphatic tissue found beneath the skin (The lymphatic tissue found beneath the skin (skin-skin-associated lymphoid tissue or SALTassociated lymphoid tissue or SALT) )

Primary and SecondaryPrimary and Secondary Lymphoid organs Lymphoid organs

Primarycentral lymphoid Primarycentral lymphoid organs organs

BONE MARROWBONE MARROW is a central organ is a central organ where all the immune cells are where all the immune cells are born and only B cells mature born and only B cells mature (process termed as (process termed as B B lymphopoiesis) lymphopoiesis)

THYMUSTHYMUS is the other central organ is the other central organ in which T cells mature (in which T cells mature (T T lymphopoiesislymphopoiesis) )

The bone marrowThe bone marrow

Bone marrow is a spongy tissue found Bone marrow is a spongy tissue found within boneswithin bonesAll blood cells are produced within the bone All blood cells are produced within the bone marrowmarrowThe bone marrow of an adult produce about The bone marrow of an adult produce about three million red blood cells and 120000 three million red blood cells and 120000 white blood cells every second white blood cells every second All these cells originate from a small All these cells originate from a small population of stem cells which may be as population of stem cells which may be as few as one in a million of the bone marrow few as one in a million of the bone marrow cells cells

ThymuThymuss

bullThe thymus is an organ located in the The thymus is an organ located in the upper chestupper chest bullImmature lymphocytes leave the bone Immature lymphocytes leave the bone marrow and find their way to the thymus marrow and find their way to the thymus where they are ldquoeducatedrdquo to become where they are ldquoeducatedrdquo to become mature T-lymphocytesmature T-lymphocytes

ThymusThymusFlat bilobed organ situated above the heart Flat bilobed organ situated above the heart

and below the thyroid glandand below the thyroid gland Each lobe is surrounded by a capsule and is Each lobe is surrounded by a capsule and is

divided into lobules divided into lobules The lobules are separated from each other by The lobules are separated from each other by

strands of connective tissue called strands of connective tissue called trabeculaetrabeculae

Each lobule is organized into two Each lobule is organized into two compartments the compartments the cortex cortex (outer (outer compartment) the compartment) the medullamedulla (inner (inner compartment) compartment)

bull Cortex and Medulla are both crisscrossed by Cortex and Medulla are both crisscrossed by a a network of stromal cellsnetwork of stromal cells composed of composed of

bull loosely packed thymic epithelial cells loosely packed thymic epithelial cells bull interdigitating dendritic cells interdigitating dendritic cells bull macrophages macrophages

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 9: Functional organization of the Immune System

Mechanism of immune Mechanism of immune responseresponse

bull Immune Immune recognition phaserecognition phase is critical in is critical in the normal functioning of the systemthe normal functioning of the system

bull This is accomplished by three sets of This is accomplished by three sets of antigen binding molecules antigen binding molecules

11 T- cell antigen receptors (TCR)T- cell antigen receptors (TCR)22 Class I and class II molecules of the Class I and class II molecules of the

MHCMHC33 B-cell antigen receptor (BCR B-cell antigen receptor (BCR

immunoglobulin)immunoglobulin)bull The The effector phaseeffector phase is mediated by a is mediated by a

variety of cells and soluble factorsvariety of cells and soluble factors

Immune SystemImmune System

Two types of immune Two types of immune systemsystem

1048698 1048698 Innate Innate immune systemimmune system

1048698 1048698 Adaptive Adaptive immune systemimmune system

Main Types of Immunity in Main Types of Immunity in ManMan

Immunity

Innate immunity

Adaptive immunity

Natural Artificial

Passive (maternal)

Active (Infection)

Passive (Serotherapy)

Active (Vaccination)

Innate ImmunityInnate Immunitybull responds immediatelyresponds immediatelybull protects the body from all foreign substancesprotects the body from all foreign substancesbull functions on two levelsfunctions on two levelsbull first line of defense ndash prevents entry of first line of defense ndash prevents entry of

pathogenspathogensbull mechanical barriersmechanical barriers

skin mucosa and secretionsskin mucosa and secretionsbull second line of defense ndash inhibits spread of second line of defense ndash inhibits spread of

pathogenpathogenbull antimicrobial proteinsantimicrobial proteinsbull phagocytes and other cellsphagocytes and other cellsbull inflammationinflammation

Three Lines of DefenseThree Lines of Defense

1st Line ndash barriers at portals of entry1st Line ndash barriers at portals of entry10486981048698primarily inborn and nonspecificprimarily inborn and nonspecific

2nd Line ndash protective cells and chemicals2nd Line ndash protective cells and chemicals10486981048698come into play when barriers are breachedcome into play when barriers are breached10486981048698primarily inborn and nonspecificprimarily inborn and nonspecific

3rd Line ndash antibodies and cytotoxic cells3rd Line ndash antibodies and cytotoxic cells10486981048698provides long-term immunity after provides long-term immunity after encountersencounters10486981048698primarily acquired and specificprimarily acquired and specific

Lines of defenseLines of defensebull 11stst lines of defense lines of defense are the physical barriers which include are the physical barriers which include

the skin urine tears ciliary elevator mucosal membrane etcthe skin urine tears ciliary elevator mucosal membrane etc

bull 22ndnd lines of defense lines of defense are the macrophage system are the macrophage system complement fever interferon and inflammation complement fever interferon and inflammation

bull 33rdrd lines of defense lines of defense aare the specific system also known re the specific system also known as acquired or adaptive immunity The specific system consists of B cells (humoral) and T cells (cell-mediated)

Physical and Chemical Physical and Chemical DefensesDefenses

First line of defense-1First line of defense-1

bull The first line of defense are The first line of defense are barrier barrier tissuestissues such as the skin that stop the such as the skin that stop the entry of pathogens into our bodiesentry of pathogens into our bodies

bull If these barrier layers are If these barrier layers are penetrated cells like penetrated cells like macrophages macrophages and neutrophilsand neutrophils engulf foreign engulf foreign organisms and kill them without the organisms and kill them without the need for antibodies need for antibodies

First Line of Defense-2First Line of Defense-2

bull SkinSkin provides an almost impenetrable provides an almost impenetrable biological barrier biological barrier

bull Lysozyme Lysozyme is an enzyme found in tears is an enzyme found in tears and saliva that and saliva that can break down foreign can break down foreign agents agents

bull The clotting of blood near open wounds The clotting of blood near open wounds prevents an open space for antigensprevents an open space for antigens

bull Mucus and cilia found in the nose and Mucus and cilia found in the nose and throat can catch foreign agents then throat can catch foreign agents then sweep them outside via sweep them outside via coughing coughing sneezing and vomiting sneezing and vomiting

bull The cell wall of plants consists of The cell wall of plants consists of fibrous fibrous proteinsproteins which provide a barrier to which provide a barrier to potential parasites (antigens) potential parasites (antigens)

A second line of defense-1A second line of defense-1

bull A second line of defense is the specific or A second line of defense is the specific or adaptive adaptive immune systemimmune system which may take days to respond which may take days to respond to a primary invasion to a primary invasion

bull The The production of antibodies and cell-mediated production of antibodies and cell-mediated responsesresponses may occur in which specific cells may occur in which specific cells recognize foreign pathogens and destroy themrecognize foreign pathogens and destroy them

bull The response is often more rapid because of the The response is often more rapid because of the activation of memory B and T cellsactivation of memory B and T cells

bull cells of the immune system interact with one cells of the immune system interact with one another by a variety of another by a variety of signal moleculessignal molecules

bull These signals may be proteins such as These signals may be proteins such as lymphokines cytokines and chemokineslymphokines cytokines and chemokines which which stimulate cells of the immune system stimulate cells of the immune system

Second Line of Defense-2Second Line of Defense-2

bull Second lines of defense deal with Second lines of defense deal with antigens that have bypassed the first antigens that have bypassed the first lines of defense lines of defense

bull InterferonsInterferons are a family of proteins that are a family of proteins that are released by a cell that is under are released by a cell that is under attack by an antigen attack by an antigen

bull One method of attacking antigens is by One method of attacking antigens is by phagocytosisphagocytosis where the contents of where the contents of the antigen are broken down by the antigen are broken down by molecules called phagocytesmolecules called phagocytes

Adaptive immunityAdaptive immunity

bull The The second levelsecond level of defence increases in of defence increases in strength and effectiveness with each strength and effectiveness with each encounter The foreign agent is recognised encounter The foreign agent is recognised in a specific manner and the immune system in a specific manner and the immune system acquires memory towards it acquires memory towards it

bull The first encounter with an antigen is The first encounter with an antigen is known as known as the primary responsethe primary response Re- Re-encounter with the same antigen causes a encounter with the same antigen causes a secondary responsesecondary response that is more rapid and that is more rapid and powerfulpowerful

Adaptive immunityAdaptive immunitybull As response produce antibodies to specific As response produce antibodies to specific

infectionsinfections

Some featuresSome features

ndash ndash MemoryMemorybull Each successive encounter with the same Each successive encounter with the same

pathogen improve the responsepathogen improve the response

ndash ndash Clonal selectionClonal selectionbull Select the best and matured immune cells Select the best and matured immune cells

to defend the organism against infectionsto defend the organism against infections

bull Whenever T cells and B cells are activated Whenever T cells and B cells are activated some become some become memory cellsmemory cells The next time The next time that an individual encounters that same that an individual encounters that same antigen the immune system is primed to antigen the immune system is primed to destroy it quickly This is destroy it quickly This is active immunityactive immunity

bull Long-term active immunityLong-term active immunity can be naturally can be naturally acquired by infection or artificially acquired acquired by infection or artificially acquired by vaccines by vaccines

bull Short-term passive immunityShort-term passive immunity can be can be transferred artificially from one individual to transferred artificially from one individual to another via antibody-rich serum another via antibody-rich serum

Active and Passive Acquired Active and Passive Acquired ImmunityImmunity

bull Active immunityActive immunity

ndash Conferred by recovery from infectious diseaseConferred by recovery from infectious disease

ndash Depends on persons own immune systemDepends on persons own immune system

ndash May be acquired artificially with May be acquired artificially with vaccinesvaccines

bull Passive immunityPassive immunity

ndash transferred from person to person through transfer of antibodiestransferred from person to person through transfer of antibodies

ndash Natural instances include antibodies passing across placenta from Natural instances include antibodies passing across placenta from mother to fetus (provides temporary protection) or through the mother to fetus (provides temporary protection) or through the milkmilk

ndash Transferred artificially Eg antibody injections for rabies anti Transferred artificially Eg antibody injections for rabies anti rhesus factor snake venom botulinun toxinrhesus factor snake venom botulinun toxin

bull Lymphatic vessels are responsible for flow of lymph Lymphatic vessels are responsible for flow of lymph within the lymphoid system within the lymphoid system

bull Plasma constantly leaks out of capillaries to deliver Plasma constantly leaks out of capillaries to deliver oxygen and nutrients to cells of the surrounding oxygen and nutrients to cells of the surrounding tissue Once in the tissue the plasma is now called tissue Once in the tissue the plasma is now called tissue fluidtissue fluid

bull While most of this tissue fluid re-enters capillaries While most of this tissue fluid re-enters capillaries and is returned directly to the bloodstream some and is returned directly to the bloodstream some fluid enters lymph vessels as fluid enters lymph vessels as lymph lymph

bull LYMPH-LYMPH- flows from the intercellular tissue spaces flows from the intercellular tissue spaces into lymphatic capillaries and then into a series of into lymphatic capillaries and then into a series of larger collecting vessels called larger collecting vessels called lymphatic vesselslymphatic vessels Lymphatic vessels converge into Lymphatic vessels converge into the thoracic ductthe thoracic duct which returns the fluid to the circulatory system by which returns the fluid to the circulatory system by dumping into the left dumping into the left subclavian vein subclavian vein

Thoracicduct

Overview of blood and lymph system and how Overview of blood and lymph system and how leukocytes travel from one system to anotherleukocytes travel from one system to another

Site of exchange between theblood and lymph systems

Lymph carrying antibodiesand immune cells collect in thoracic duct where the lymph empties back into the blood circulatory system

Immune cells travel back and forth from Immune cells travel back and forth from the blood and lymph circulatory systems the blood and lymph circulatory systems and interact with extra-vascular tissues and interact with extra-vascular tissues

in the process--in the process--extravasationextravasation

muscle

Lymphatic vessels Lymphatic vessels

The organs of the The organs of the immune system immune system

Kinds of lymphoid Kinds of lymphoid OrgansOrgans

Primarycentral lymphoid organsPrimarycentral lymphoid organs ndash bone marrow bone marrow ndash thymus thymus

Secondary peripheral lymphoid tissueSecondary peripheral lymphoid tissuendash lymph nodes lymph nodes ndash spleenspleenndash mucosa-associated lymphoid tissuemucosa-associated lymphoid tissue

Kinds of Lymphoid Organs Kinds of Lymphoid Organs The Lymphoid

Organs

Primary or Central organs

Secondary or Peripheral organs

1Bone marrow2Thymus gland3Bursa of fabricius

1Lymp nodes 2Spleen

3Diffuse lymphoid tissues

bull The The bone marrowbone marrow and the and the thymusthymus constitute constitute the primary lymphoid organsthe primary lymphoid organs

bull Both Both B-lymphocytesB-lymphocytes and and T-lymphocytesT-lymphocytes are are produced from stem cells in the bone produced from stem cells in the bone marrow marrow B-lymphocytes mature in the B-lymphocytes mature in the bone marrow while T-lymphocytes bone marrow while T-lymphocytes migrate to the thymus and mature migrate to the thymus and mature therethere

bull After maturation both B-lymphocytes and T-After maturation both B-lymphocytes and T-lymphocytes circulate through and lymphocytes circulate through and accumulate in accumulate in secondary lymphoid organssecondary lymphoid organs

bull The secondary lymphoid organs include lymph nodes The secondary lymphoid organs include lymph nodes and the spleen as well as lymphoid tissues and the spleen as well as lymphoid tissues

bull The lymphoid tissues include The lymphoid tissues include the tonsils the the tonsils the appendix the Peyers patchesappendix the Peyers patches in the lining of the in the lining of the small intestines (small intestines (gut-associated lymphoid tissue or gut-associated lymphoid tissue or GALTGALT) )

bull The lymphoid tissue found beneath the mucous The lymphoid tissue found beneath the mucous membranes of the bronchi (membranes of the bronchi (bronchial-associated bronchial-associated lymphoid tissue or BALTlymphoid tissue or BALT) )

bull The lymphatic tissue found in the mucous The lymphatic tissue found in the mucous membranes (membranes (mucosa-associated lymphoid tissue or mucosa-associated lymphoid tissue or MALTMALT))

bull The lymphatic tissue found beneath the skin (The lymphatic tissue found beneath the skin (skin-skin-associated lymphoid tissue or SALTassociated lymphoid tissue or SALT) )

Primary and SecondaryPrimary and Secondary Lymphoid organs Lymphoid organs

Primarycentral lymphoid Primarycentral lymphoid organs organs

BONE MARROWBONE MARROW is a central organ is a central organ where all the immune cells are where all the immune cells are born and only B cells mature born and only B cells mature (process termed as (process termed as B B lymphopoiesis) lymphopoiesis)

THYMUSTHYMUS is the other central organ is the other central organ in which T cells mature (in which T cells mature (T T lymphopoiesislymphopoiesis) )

The bone marrowThe bone marrow

Bone marrow is a spongy tissue found Bone marrow is a spongy tissue found within boneswithin bonesAll blood cells are produced within the bone All blood cells are produced within the bone marrowmarrowThe bone marrow of an adult produce about The bone marrow of an adult produce about three million red blood cells and 120000 three million red blood cells and 120000 white blood cells every second white blood cells every second All these cells originate from a small All these cells originate from a small population of stem cells which may be as population of stem cells which may be as few as one in a million of the bone marrow few as one in a million of the bone marrow cells cells

ThymuThymuss

bullThe thymus is an organ located in the The thymus is an organ located in the upper chestupper chest bullImmature lymphocytes leave the bone Immature lymphocytes leave the bone marrow and find their way to the thymus marrow and find their way to the thymus where they are ldquoeducatedrdquo to become where they are ldquoeducatedrdquo to become mature T-lymphocytesmature T-lymphocytes

ThymusThymusFlat bilobed organ situated above the heart Flat bilobed organ situated above the heart

and below the thyroid glandand below the thyroid gland Each lobe is surrounded by a capsule and is Each lobe is surrounded by a capsule and is

divided into lobules divided into lobules The lobules are separated from each other by The lobules are separated from each other by

strands of connective tissue called strands of connective tissue called trabeculaetrabeculae

Each lobule is organized into two Each lobule is organized into two compartments the compartments the cortex cortex (outer (outer compartment) the compartment) the medullamedulla (inner (inner compartment) compartment)

bull Cortex and Medulla are both crisscrossed by Cortex and Medulla are both crisscrossed by a a network of stromal cellsnetwork of stromal cells composed of composed of

bull loosely packed thymic epithelial cells loosely packed thymic epithelial cells bull interdigitating dendritic cells interdigitating dendritic cells bull macrophages macrophages

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 10: Functional organization of the Immune System

Immune SystemImmune System

Two types of immune Two types of immune systemsystem

1048698 1048698 Innate Innate immune systemimmune system

1048698 1048698 Adaptive Adaptive immune systemimmune system

Main Types of Immunity in Main Types of Immunity in ManMan

Immunity

Innate immunity

Adaptive immunity

Natural Artificial

Passive (maternal)

Active (Infection)

Passive (Serotherapy)

Active (Vaccination)

Innate ImmunityInnate Immunitybull responds immediatelyresponds immediatelybull protects the body from all foreign substancesprotects the body from all foreign substancesbull functions on two levelsfunctions on two levelsbull first line of defense ndash prevents entry of first line of defense ndash prevents entry of

pathogenspathogensbull mechanical barriersmechanical barriers

skin mucosa and secretionsskin mucosa and secretionsbull second line of defense ndash inhibits spread of second line of defense ndash inhibits spread of

pathogenpathogenbull antimicrobial proteinsantimicrobial proteinsbull phagocytes and other cellsphagocytes and other cellsbull inflammationinflammation

Three Lines of DefenseThree Lines of Defense

1st Line ndash barriers at portals of entry1st Line ndash barriers at portals of entry10486981048698primarily inborn and nonspecificprimarily inborn and nonspecific

2nd Line ndash protective cells and chemicals2nd Line ndash protective cells and chemicals10486981048698come into play when barriers are breachedcome into play when barriers are breached10486981048698primarily inborn and nonspecificprimarily inborn and nonspecific

3rd Line ndash antibodies and cytotoxic cells3rd Line ndash antibodies and cytotoxic cells10486981048698provides long-term immunity after provides long-term immunity after encountersencounters10486981048698primarily acquired and specificprimarily acquired and specific

Lines of defenseLines of defensebull 11stst lines of defense lines of defense are the physical barriers which include are the physical barriers which include

the skin urine tears ciliary elevator mucosal membrane etcthe skin urine tears ciliary elevator mucosal membrane etc

bull 22ndnd lines of defense lines of defense are the macrophage system are the macrophage system complement fever interferon and inflammation complement fever interferon and inflammation

bull 33rdrd lines of defense lines of defense aare the specific system also known re the specific system also known as acquired or adaptive immunity The specific system consists of B cells (humoral) and T cells (cell-mediated)

Physical and Chemical Physical and Chemical DefensesDefenses

First line of defense-1First line of defense-1

bull The first line of defense are The first line of defense are barrier barrier tissuestissues such as the skin that stop the such as the skin that stop the entry of pathogens into our bodiesentry of pathogens into our bodies

bull If these barrier layers are If these barrier layers are penetrated cells like penetrated cells like macrophages macrophages and neutrophilsand neutrophils engulf foreign engulf foreign organisms and kill them without the organisms and kill them without the need for antibodies need for antibodies

First Line of Defense-2First Line of Defense-2

bull SkinSkin provides an almost impenetrable provides an almost impenetrable biological barrier biological barrier

bull Lysozyme Lysozyme is an enzyme found in tears is an enzyme found in tears and saliva that and saliva that can break down foreign can break down foreign agents agents

bull The clotting of blood near open wounds The clotting of blood near open wounds prevents an open space for antigensprevents an open space for antigens

bull Mucus and cilia found in the nose and Mucus and cilia found in the nose and throat can catch foreign agents then throat can catch foreign agents then sweep them outside via sweep them outside via coughing coughing sneezing and vomiting sneezing and vomiting

bull The cell wall of plants consists of The cell wall of plants consists of fibrous fibrous proteinsproteins which provide a barrier to which provide a barrier to potential parasites (antigens) potential parasites (antigens)

A second line of defense-1A second line of defense-1

bull A second line of defense is the specific or A second line of defense is the specific or adaptive adaptive immune systemimmune system which may take days to respond which may take days to respond to a primary invasion to a primary invasion

bull The The production of antibodies and cell-mediated production of antibodies and cell-mediated responsesresponses may occur in which specific cells may occur in which specific cells recognize foreign pathogens and destroy themrecognize foreign pathogens and destroy them

bull The response is often more rapid because of the The response is often more rapid because of the activation of memory B and T cellsactivation of memory B and T cells

bull cells of the immune system interact with one cells of the immune system interact with one another by a variety of another by a variety of signal moleculessignal molecules

bull These signals may be proteins such as These signals may be proteins such as lymphokines cytokines and chemokineslymphokines cytokines and chemokines which which stimulate cells of the immune system stimulate cells of the immune system

Second Line of Defense-2Second Line of Defense-2

bull Second lines of defense deal with Second lines of defense deal with antigens that have bypassed the first antigens that have bypassed the first lines of defense lines of defense

bull InterferonsInterferons are a family of proteins that are a family of proteins that are released by a cell that is under are released by a cell that is under attack by an antigen attack by an antigen

bull One method of attacking antigens is by One method of attacking antigens is by phagocytosisphagocytosis where the contents of where the contents of the antigen are broken down by the antigen are broken down by molecules called phagocytesmolecules called phagocytes

Adaptive immunityAdaptive immunity

bull The The second levelsecond level of defence increases in of defence increases in strength and effectiveness with each strength and effectiveness with each encounter The foreign agent is recognised encounter The foreign agent is recognised in a specific manner and the immune system in a specific manner and the immune system acquires memory towards it acquires memory towards it

bull The first encounter with an antigen is The first encounter with an antigen is known as known as the primary responsethe primary response Re- Re-encounter with the same antigen causes a encounter with the same antigen causes a secondary responsesecondary response that is more rapid and that is more rapid and powerfulpowerful

Adaptive immunityAdaptive immunitybull As response produce antibodies to specific As response produce antibodies to specific

infectionsinfections

Some featuresSome features

ndash ndash MemoryMemorybull Each successive encounter with the same Each successive encounter with the same

pathogen improve the responsepathogen improve the response

ndash ndash Clonal selectionClonal selectionbull Select the best and matured immune cells Select the best and matured immune cells

to defend the organism against infectionsto defend the organism against infections

bull Whenever T cells and B cells are activated Whenever T cells and B cells are activated some become some become memory cellsmemory cells The next time The next time that an individual encounters that same that an individual encounters that same antigen the immune system is primed to antigen the immune system is primed to destroy it quickly This is destroy it quickly This is active immunityactive immunity

bull Long-term active immunityLong-term active immunity can be naturally can be naturally acquired by infection or artificially acquired acquired by infection or artificially acquired by vaccines by vaccines

bull Short-term passive immunityShort-term passive immunity can be can be transferred artificially from one individual to transferred artificially from one individual to another via antibody-rich serum another via antibody-rich serum

Active and Passive Acquired Active and Passive Acquired ImmunityImmunity

bull Active immunityActive immunity

ndash Conferred by recovery from infectious diseaseConferred by recovery from infectious disease

ndash Depends on persons own immune systemDepends on persons own immune system

ndash May be acquired artificially with May be acquired artificially with vaccinesvaccines

bull Passive immunityPassive immunity

ndash transferred from person to person through transfer of antibodiestransferred from person to person through transfer of antibodies

ndash Natural instances include antibodies passing across placenta from Natural instances include antibodies passing across placenta from mother to fetus (provides temporary protection) or through the mother to fetus (provides temporary protection) or through the milkmilk

ndash Transferred artificially Eg antibody injections for rabies anti Transferred artificially Eg antibody injections for rabies anti rhesus factor snake venom botulinun toxinrhesus factor snake venom botulinun toxin

bull Lymphatic vessels are responsible for flow of lymph Lymphatic vessels are responsible for flow of lymph within the lymphoid system within the lymphoid system

bull Plasma constantly leaks out of capillaries to deliver Plasma constantly leaks out of capillaries to deliver oxygen and nutrients to cells of the surrounding oxygen and nutrients to cells of the surrounding tissue Once in the tissue the plasma is now called tissue Once in the tissue the plasma is now called tissue fluidtissue fluid

bull While most of this tissue fluid re-enters capillaries While most of this tissue fluid re-enters capillaries and is returned directly to the bloodstream some and is returned directly to the bloodstream some fluid enters lymph vessels as fluid enters lymph vessels as lymph lymph

bull LYMPH-LYMPH- flows from the intercellular tissue spaces flows from the intercellular tissue spaces into lymphatic capillaries and then into a series of into lymphatic capillaries and then into a series of larger collecting vessels called larger collecting vessels called lymphatic vesselslymphatic vessels Lymphatic vessels converge into Lymphatic vessels converge into the thoracic ductthe thoracic duct which returns the fluid to the circulatory system by which returns the fluid to the circulatory system by dumping into the left dumping into the left subclavian vein subclavian vein

Thoracicduct

Overview of blood and lymph system and how Overview of blood and lymph system and how leukocytes travel from one system to anotherleukocytes travel from one system to another

Site of exchange between theblood and lymph systems

Lymph carrying antibodiesand immune cells collect in thoracic duct where the lymph empties back into the blood circulatory system

Immune cells travel back and forth from Immune cells travel back and forth from the blood and lymph circulatory systems the blood and lymph circulatory systems and interact with extra-vascular tissues and interact with extra-vascular tissues

in the process--in the process--extravasationextravasation

muscle

Lymphatic vessels Lymphatic vessels

The organs of the The organs of the immune system immune system

Kinds of lymphoid Kinds of lymphoid OrgansOrgans

Primarycentral lymphoid organsPrimarycentral lymphoid organs ndash bone marrow bone marrow ndash thymus thymus

Secondary peripheral lymphoid tissueSecondary peripheral lymphoid tissuendash lymph nodes lymph nodes ndash spleenspleenndash mucosa-associated lymphoid tissuemucosa-associated lymphoid tissue

Kinds of Lymphoid Organs Kinds of Lymphoid Organs The Lymphoid

Organs

Primary or Central organs

Secondary or Peripheral organs

1Bone marrow2Thymus gland3Bursa of fabricius

1Lymp nodes 2Spleen

3Diffuse lymphoid tissues

bull The The bone marrowbone marrow and the and the thymusthymus constitute constitute the primary lymphoid organsthe primary lymphoid organs

bull Both Both B-lymphocytesB-lymphocytes and and T-lymphocytesT-lymphocytes are are produced from stem cells in the bone produced from stem cells in the bone marrow marrow B-lymphocytes mature in the B-lymphocytes mature in the bone marrow while T-lymphocytes bone marrow while T-lymphocytes migrate to the thymus and mature migrate to the thymus and mature therethere

bull After maturation both B-lymphocytes and T-After maturation both B-lymphocytes and T-lymphocytes circulate through and lymphocytes circulate through and accumulate in accumulate in secondary lymphoid organssecondary lymphoid organs

bull The secondary lymphoid organs include lymph nodes The secondary lymphoid organs include lymph nodes and the spleen as well as lymphoid tissues and the spleen as well as lymphoid tissues

bull The lymphoid tissues include The lymphoid tissues include the tonsils the the tonsils the appendix the Peyers patchesappendix the Peyers patches in the lining of the in the lining of the small intestines (small intestines (gut-associated lymphoid tissue or gut-associated lymphoid tissue or GALTGALT) )

bull The lymphoid tissue found beneath the mucous The lymphoid tissue found beneath the mucous membranes of the bronchi (membranes of the bronchi (bronchial-associated bronchial-associated lymphoid tissue or BALTlymphoid tissue or BALT) )

bull The lymphatic tissue found in the mucous The lymphatic tissue found in the mucous membranes (membranes (mucosa-associated lymphoid tissue or mucosa-associated lymphoid tissue or MALTMALT))

bull The lymphatic tissue found beneath the skin (The lymphatic tissue found beneath the skin (skin-skin-associated lymphoid tissue or SALTassociated lymphoid tissue or SALT) )

Primary and SecondaryPrimary and Secondary Lymphoid organs Lymphoid organs

Primarycentral lymphoid Primarycentral lymphoid organs organs

BONE MARROWBONE MARROW is a central organ is a central organ where all the immune cells are where all the immune cells are born and only B cells mature born and only B cells mature (process termed as (process termed as B B lymphopoiesis) lymphopoiesis)

THYMUSTHYMUS is the other central organ is the other central organ in which T cells mature (in which T cells mature (T T lymphopoiesislymphopoiesis) )

The bone marrowThe bone marrow

Bone marrow is a spongy tissue found Bone marrow is a spongy tissue found within boneswithin bonesAll blood cells are produced within the bone All blood cells are produced within the bone marrowmarrowThe bone marrow of an adult produce about The bone marrow of an adult produce about three million red blood cells and 120000 three million red blood cells and 120000 white blood cells every second white blood cells every second All these cells originate from a small All these cells originate from a small population of stem cells which may be as population of stem cells which may be as few as one in a million of the bone marrow few as one in a million of the bone marrow cells cells

ThymuThymuss

bullThe thymus is an organ located in the The thymus is an organ located in the upper chestupper chest bullImmature lymphocytes leave the bone Immature lymphocytes leave the bone marrow and find their way to the thymus marrow and find their way to the thymus where they are ldquoeducatedrdquo to become where they are ldquoeducatedrdquo to become mature T-lymphocytesmature T-lymphocytes

ThymusThymusFlat bilobed organ situated above the heart Flat bilobed organ situated above the heart

and below the thyroid glandand below the thyroid gland Each lobe is surrounded by a capsule and is Each lobe is surrounded by a capsule and is

divided into lobules divided into lobules The lobules are separated from each other by The lobules are separated from each other by

strands of connective tissue called strands of connective tissue called trabeculaetrabeculae

Each lobule is organized into two Each lobule is organized into two compartments the compartments the cortex cortex (outer (outer compartment) the compartment) the medullamedulla (inner (inner compartment) compartment)

bull Cortex and Medulla are both crisscrossed by Cortex and Medulla are both crisscrossed by a a network of stromal cellsnetwork of stromal cells composed of composed of

bull loosely packed thymic epithelial cells loosely packed thymic epithelial cells bull interdigitating dendritic cells interdigitating dendritic cells bull macrophages macrophages

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 11: Functional organization of the Immune System

Main Types of Immunity in Main Types of Immunity in ManMan

Immunity

Innate immunity

Adaptive immunity

Natural Artificial

Passive (maternal)

Active (Infection)

Passive (Serotherapy)

Active (Vaccination)

Innate ImmunityInnate Immunitybull responds immediatelyresponds immediatelybull protects the body from all foreign substancesprotects the body from all foreign substancesbull functions on two levelsfunctions on two levelsbull first line of defense ndash prevents entry of first line of defense ndash prevents entry of

pathogenspathogensbull mechanical barriersmechanical barriers

skin mucosa and secretionsskin mucosa and secretionsbull second line of defense ndash inhibits spread of second line of defense ndash inhibits spread of

pathogenpathogenbull antimicrobial proteinsantimicrobial proteinsbull phagocytes and other cellsphagocytes and other cellsbull inflammationinflammation

Three Lines of DefenseThree Lines of Defense

1st Line ndash barriers at portals of entry1st Line ndash barriers at portals of entry10486981048698primarily inborn and nonspecificprimarily inborn and nonspecific

2nd Line ndash protective cells and chemicals2nd Line ndash protective cells and chemicals10486981048698come into play when barriers are breachedcome into play when barriers are breached10486981048698primarily inborn and nonspecificprimarily inborn and nonspecific

3rd Line ndash antibodies and cytotoxic cells3rd Line ndash antibodies and cytotoxic cells10486981048698provides long-term immunity after provides long-term immunity after encountersencounters10486981048698primarily acquired and specificprimarily acquired and specific

Lines of defenseLines of defensebull 11stst lines of defense lines of defense are the physical barriers which include are the physical barriers which include

the skin urine tears ciliary elevator mucosal membrane etcthe skin urine tears ciliary elevator mucosal membrane etc

bull 22ndnd lines of defense lines of defense are the macrophage system are the macrophage system complement fever interferon and inflammation complement fever interferon and inflammation

bull 33rdrd lines of defense lines of defense aare the specific system also known re the specific system also known as acquired or adaptive immunity The specific system consists of B cells (humoral) and T cells (cell-mediated)

Physical and Chemical Physical and Chemical DefensesDefenses

First line of defense-1First line of defense-1

bull The first line of defense are The first line of defense are barrier barrier tissuestissues such as the skin that stop the such as the skin that stop the entry of pathogens into our bodiesentry of pathogens into our bodies

bull If these barrier layers are If these barrier layers are penetrated cells like penetrated cells like macrophages macrophages and neutrophilsand neutrophils engulf foreign engulf foreign organisms and kill them without the organisms and kill them without the need for antibodies need for antibodies

First Line of Defense-2First Line of Defense-2

bull SkinSkin provides an almost impenetrable provides an almost impenetrable biological barrier biological barrier

bull Lysozyme Lysozyme is an enzyme found in tears is an enzyme found in tears and saliva that and saliva that can break down foreign can break down foreign agents agents

bull The clotting of blood near open wounds The clotting of blood near open wounds prevents an open space for antigensprevents an open space for antigens

bull Mucus and cilia found in the nose and Mucus and cilia found in the nose and throat can catch foreign agents then throat can catch foreign agents then sweep them outside via sweep them outside via coughing coughing sneezing and vomiting sneezing and vomiting

bull The cell wall of plants consists of The cell wall of plants consists of fibrous fibrous proteinsproteins which provide a barrier to which provide a barrier to potential parasites (antigens) potential parasites (antigens)

A second line of defense-1A second line of defense-1

bull A second line of defense is the specific or A second line of defense is the specific or adaptive adaptive immune systemimmune system which may take days to respond which may take days to respond to a primary invasion to a primary invasion

bull The The production of antibodies and cell-mediated production of antibodies and cell-mediated responsesresponses may occur in which specific cells may occur in which specific cells recognize foreign pathogens and destroy themrecognize foreign pathogens and destroy them

bull The response is often more rapid because of the The response is often more rapid because of the activation of memory B and T cellsactivation of memory B and T cells

bull cells of the immune system interact with one cells of the immune system interact with one another by a variety of another by a variety of signal moleculessignal molecules

bull These signals may be proteins such as These signals may be proteins such as lymphokines cytokines and chemokineslymphokines cytokines and chemokines which which stimulate cells of the immune system stimulate cells of the immune system

Second Line of Defense-2Second Line of Defense-2

bull Second lines of defense deal with Second lines of defense deal with antigens that have bypassed the first antigens that have bypassed the first lines of defense lines of defense

bull InterferonsInterferons are a family of proteins that are a family of proteins that are released by a cell that is under are released by a cell that is under attack by an antigen attack by an antigen

bull One method of attacking antigens is by One method of attacking antigens is by phagocytosisphagocytosis where the contents of where the contents of the antigen are broken down by the antigen are broken down by molecules called phagocytesmolecules called phagocytes

Adaptive immunityAdaptive immunity

bull The The second levelsecond level of defence increases in of defence increases in strength and effectiveness with each strength and effectiveness with each encounter The foreign agent is recognised encounter The foreign agent is recognised in a specific manner and the immune system in a specific manner and the immune system acquires memory towards it acquires memory towards it

bull The first encounter with an antigen is The first encounter with an antigen is known as known as the primary responsethe primary response Re- Re-encounter with the same antigen causes a encounter with the same antigen causes a secondary responsesecondary response that is more rapid and that is more rapid and powerfulpowerful

Adaptive immunityAdaptive immunitybull As response produce antibodies to specific As response produce antibodies to specific

infectionsinfections

Some featuresSome features

ndash ndash MemoryMemorybull Each successive encounter with the same Each successive encounter with the same

pathogen improve the responsepathogen improve the response

ndash ndash Clonal selectionClonal selectionbull Select the best and matured immune cells Select the best and matured immune cells

to defend the organism against infectionsto defend the organism against infections

bull Whenever T cells and B cells are activated Whenever T cells and B cells are activated some become some become memory cellsmemory cells The next time The next time that an individual encounters that same that an individual encounters that same antigen the immune system is primed to antigen the immune system is primed to destroy it quickly This is destroy it quickly This is active immunityactive immunity

bull Long-term active immunityLong-term active immunity can be naturally can be naturally acquired by infection or artificially acquired acquired by infection or artificially acquired by vaccines by vaccines

bull Short-term passive immunityShort-term passive immunity can be can be transferred artificially from one individual to transferred artificially from one individual to another via antibody-rich serum another via antibody-rich serum

Active and Passive Acquired Active and Passive Acquired ImmunityImmunity

bull Active immunityActive immunity

ndash Conferred by recovery from infectious diseaseConferred by recovery from infectious disease

ndash Depends on persons own immune systemDepends on persons own immune system

ndash May be acquired artificially with May be acquired artificially with vaccinesvaccines

bull Passive immunityPassive immunity

ndash transferred from person to person through transfer of antibodiestransferred from person to person through transfer of antibodies

ndash Natural instances include antibodies passing across placenta from Natural instances include antibodies passing across placenta from mother to fetus (provides temporary protection) or through the mother to fetus (provides temporary protection) or through the milkmilk

ndash Transferred artificially Eg antibody injections for rabies anti Transferred artificially Eg antibody injections for rabies anti rhesus factor snake venom botulinun toxinrhesus factor snake venom botulinun toxin

bull Lymphatic vessels are responsible for flow of lymph Lymphatic vessels are responsible for flow of lymph within the lymphoid system within the lymphoid system

bull Plasma constantly leaks out of capillaries to deliver Plasma constantly leaks out of capillaries to deliver oxygen and nutrients to cells of the surrounding oxygen and nutrients to cells of the surrounding tissue Once in the tissue the plasma is now called tissue Once in the tissue the plasma is now called tissue fluidtissue fluid

bull While most of this tissue fluid re-enters capillaries While most of this tissue fluid re-enters capillaries and is returned directly to the bloodstream some and is returned directly to the bloodstream some fluid enters lymph vessels as fluid enters lymph vessels as lymph lymph

bull LYMPH-LYMPH- flows from the intercellular tissue spaces flows from the intercellular tissue spaces into lymphatic capillaries and then into a series of into lymphatic capillaries and then into a series of larger collecting vessels called larger collecting vessels called lymphatic vesselslymphatic vessels Lymphatic vessels converge into Lymphatic vessels converge into the thoracic ductthe thoracic duct which returns the fluid to the circulatory system by which returns the fluid to the circulatory system by dumping into the left dumping into the left subclavian vein subclavian vein

Thoracicduct

Overview of blood and lymph system and how Overview of blood and lymph system and how leukocytes travel from one system to anotherleukocytes travel from one system to another

Site of exchange between theblood and lymph systems

Lymph carrying antibodiesand immune cells collect in thoracic duct where the lymph empties back into the blood circulatory system

Immune cells travel back and forth from Immune cells travel back and forth from the blood and lymph circulatory systems the blood and lymph circulatory systems and interact with extra-vascular tissues and interact with extra-vascular tissues

in the process--in the process--extravasationextravasation

muscle

Lymphatic vessels Lymphatic vessels

The organs of the The organs of the immune system immune system

Kinds of lymphoid Kinds of lymphoid OrgansOrgans

Primarycentral lymphoid organsPrimarycentral lymphoid organs ndash bone marrow bone marrow ndash thymus thymus

Secondary peripheral lymphoid tissueSecondary peripheral lymphoid tissuendash lymph nodes lymph nodes ndash spleenspleenndash mucosa-associated lymphoid tissuemucosa-associated lymphoid tissue

Kinds of Lymphoid Organs Kinds of Lymphoid Organs The Lymphoid

Organs

Primary or Central organs

Secondary or Peripheral organs

1Bone marrow2Thymus gland3Bursa of fabricius

1Lymp nodes 2Spleen

3Diffuse lymphoid tissues

bull The The bone marrowbone marrow and the and the thymusthymus constitute constitute the primary lymphoid organsthe primary lymphoid organs

bull Both Both B-lymphocytesB-lymphocytes and and T-lymphocytesT-lymphocytes are are produced from stem cells in the bone produced from stem cells in the bone marrow marrow B-lymphocytes mature in the B-lymphocytes mature in the bone marrow while T-lymphocytes bone marrow while T-lymphocytes migrate to the thymus and mature migrate to the thymus and mature therethere

bull After maturation both B-lymphocytes and T-After maturation both B-lymphocytes and T-lymphocytes circulate through and lymphocytes circulate through and accumulate in accumulate in secondary lymphoid organssecondary lymphoid organs

bull The secondary lymphoid organs include lymph nodes The secondary lymphoid organs include lymph nodes and the spleen as well as lymphoid tissues and the spleen as well as lymphoid tissues

bull The lymphoid tissues include The lymphoid tissues include the tonsils the the tonsils the appendix the Peyers patchesappendix the Peyers patches in the lining of the in the lining of the small intestines (small intestines (gut-associated lymphoid tissue or gut-associated lymphoid tissue or GALTGALT) )

bull The lymphoid tissue found beneath the mucous The lymphoid tissue found beneath the mucous membranes of the bronchi (membranes of the bronchi (bronchial-associated bronchial-associated lymphoid tissue or BALTlymphoid tissue or BALT) )

bull The lymphatic tissue found in the mucous The lymphatic tissue found in the mucous membranes (membranes (mucosa-associated lymphoid tissue or mucosa-associated lymphoid tissue or MALTMALT))

bull The lymphatic tissue found beneath the skin (The lymphatic tissue found beneath the skin (skin-skin-associated lymphoid tissue or SALTassociated lymphoid tissue or SALT) )

Primary and SecondaryPrimary and Secondary Lymphoid organs Lymphoid organs

Primarycentral lymphoid Primarycentral lymphoid organs organs

BONE MARROWBONE MARROW is a central organ is a central organ where all the immune cells are where all the immune cells are born and only B cells mature born and only B cells mature (process termed as (process termed as B B lymphopoiesis) lymphopoiesis)

THYMUSTHYMUS is the other central organ is the other central organ in which T cells mature (in which T cells mature (T T lymphopoiesislymphopoiesis) )

The bone marrowThe bone marrow

Bone marrow is a spongy tissue found Bone marrow is a spongy tissue found within boneswithin bonesAll blood cells are produced within the bone All blood cells are produced within the bone marrowmarrowThe bone marrow of an adult produce about The bone marrow of an adult produce about three million red blood cells and 120000 three million red blood cells and 120000 white blood cells every second white blood cells every second All these cells originate from a small All these cells originate from a small population of stem cells which may be as population of stem cells which may be as few as one in a million of the bone marrow few as one in a million of the bone marrow cells cells

ThymuThymuss

bullThe thymus is an organ located in the The thymus is an organ located in the upper chestupper chest bullImmature lymphocytes leave the bone Immature lymphocytes leave the bone marrow and find their way to the thymus marrow and find their way to the thymus where they are ldquoeducatedrdquo to become where they are ldquoeducatedrdquo to become mature T-lymphocytesmature T-lymphocytes

ThymusThymusFlat bilobed organ situated above the heart Flat bilobed organ situated above the heart

and below the thyroid glandand below the thyroid gland Each lobe is surrounded by a capsule and is Each lobe is surrounded by a capsule and is

divided into lobules divided into lobules The lobules are separated from each other by The lobules are separated from each other by

strands of connective tissue called strands of connective tissue called trabeculaetrabeculae

Each lobule is organized into two Each lobule is organized into two compartments the compartments the cortex cortex (outer (outer compartment) the compartment) the medullamedulla (inner (inner compartment) compartment)

bull Cortex and Medulla are both crisscrossed by Cortex and Medulla are both crisscrossed by a a network of stromal cellsnetwork of stromal cells composed of composed of

bull loosely packed thymic epithelial cells loosely packed thymic epithelial cells bull interdigitating dendritic cells interdigitating dendritic cells bull macrophages macrophages

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 12: Functional organization of the Immune System

Innate ImmunityInnate Immunitybull responds immediatelyresponds immediatelybull protects the body from all foreign substancesprotects the body from all foreign substancesbull functions on two levelsfunctions on two levelsbull first line of defense ndash prevents entry of first line of defense ndash prevents entry of

pathogenspathogensbull mechanical barriersmechanical barriers

skin mucosa and secretionsskin mucosa and secretionsbull second line of defense ndash inhibits spread of second line of defense ndash inhibits spread of

pathogenpathogenbull antimicrobial proteinsantimicrobial proteinsbull phagocytes and other cellsphagocytes and other cellsbull inflammationinflammation

Three Lines of DefenseThree Lines of Defense

1st Line ndash barriers at portals of entry1st Line ndash barriers at portals of entry10486981048698primarily inborn and nonspecificprimarily inborn and nonspecific

2nd Line ndash protective cells and chemicals2nd Line ndash protective cells and chemicals10486981048698come into play when barriers are breachedcome into play when barriers are breached10486981048698primarily inborn and nonspecificprimarily inborn and nonspecific

3rd Line ndash antibodies and cytotoxic cells3rd Line ndash antibodies and cytotoxic cells10486981048698provides long-term immunity after provides long-term immunity after encountersencounters10486981048698primarily acquired and specificprimarily acquired and specific

Lines of defenseLines of defensebull 11stst lines of defense lines of defense are the physical barriers which include are the physical barriers which include

the skin urine tears ciliary elevator mucosal membrane etcthe skin urine tears ciliary elevator mucosal membrane etc

bull 22ndnd lines of defense lines of defense are the macrophage system are the macrophage system complement fever interferon and inflammation complement fever interferon and inflammation

bull 33rdrd lines of defense lines of defense aare the specific system also known re the specific system also known as acquired or adaptive immunity The specific system consists of B cells (humoral) and T cells (cell-mediated)

Physical and Chemical Physical and Chemical DefensesDefenses

First line of defense-1First line of defense-1

bull The first line of defense are The first line of defense are barrier barrier tissuestissues such as the skin that stop the such as the skin that stop the entry of pathogens into our bodiesentry of pathogens into our bodies

bull If these barrier layers are If these barrier layers are penetrated cells like penetrated cells like macrophages macrophages and neutrophilsand neutrophils engulf foreign engulf foreign organisms and kill them without the organisms and kill them without the need for antibodies need for antibodies

First Line of Defense-2First Line of Defense-2

bull SkinSkin provides an almost impenetrable provides an almost impenetrable biological barrier biological barrier

bull Lysozyme Lysozyme is an enzyme found in tears is an enzyme found in tears and saliva that and saliva that can break down foreign can break down foreign agents agents

bull The clotting of blood near open wounds The clotting of blood near open wounds prevents an open space for antigensprevents an open space for antigens

bull Mucus and cilia found in the nose and Mucus and cilia found in the nose and throat can catch foreign agents then throat can catch foreign agents then sweep them outside via sweep them outside via coughing coughing sneezing and vomiting sneezing and vomiting

bull The cell wall of plants consists of The cell wall of plants consists of fibrous fibrous proteinsproteins which provide a barrier to which provide a barrier to potential parasites (antigens) potential parasites (antigens)

A second line of defense-1A second line of defense-1

bull A second line of defense is the specific or A second line of defense is the specific or adaptive adaptive immune systemimmune system which may take days to respond which may take days to respond to a primary invasion to a primary invasion

bull The The production of antibodies and cell-mediated production of antibodies and cell-mediated responsesresponses may occur in which specific cells may occur in which specific cells recognize foreign pathogens and destroy themrecognize foreign pathogens and destroy them

bull The response is often more rapid because of the The response is often more rapid because of the activation of memory B and T cellsactivation of memory B and T cells

bull cells of the immune system interact with one cells of the immune system interact with one another by a variety of another by a variety of signal moleculessignal molecules

bull These signals may be proteins such as These signals may be proteins such as lymphokines cytokines and chemokineslymphokines cytokines and chemokines which which stimulate cells of the immune system stimulate cells of the immune system

Second Line of Defense-2Second Line of Defense-2

bull Second lines of defense deal with Second lines of defense deal with antigens that have bypassed the first antigens that have bypassed the first lines of defense lines of defense

bull InterferonsInterferons are a family of proteins that are a family of proteins that are released by a cell that is under are released by a cell that is under attack by an antigen attack by an antigen

bull One method of attacking antigens is by One method of attacking antigens is by phagocytosisphagocytosis where the contents of where the contents of the antigen are broken down by the antigen are broken down by molecules called phagocytesmolecules called phagocytes

Adaptive immunityAdaptive immunity

bull The The second levelsecond level of defence increases in of defence increases in strength and effectiveness with each strength and effectiveness with each encounter The foreign agent is recognised encounter The foreign agent is recognised in a specific manner and the immune system in a specific manner and the immune system acquires memory towards it acquires memory towards it

bull The first encounter with an antigen is The first encounter with an antigen is known as known as the primary responsethe primary response Re- Re-encounter with the same antigen causes a encounter with the same antigen causes a secondary responsesecondary response that is more rapid and that is more rapid and powerfulpowerful

Adaptive immunityAdaptive immunitybull As response produce antibodies to specific As response produce antibodies to specific

infectionsinfections

Some featuresSome features

ndash ndash MemoryMemorybull Each successive encounter with the same Each successive encounter with the same

pathogen improve the responsepathogen improve the response

ndash ndash Clonal selectionClonal selectionbull Select the best and matured immune cells Select the best and matured immune cells

to defend the organism against infectionsto defend the organism against infections

bull Whenever T cells and B cells are activated Whenever T cells and B cells are activated some become some become memory cellsmemory cells The next time The next time that an individual encounters that same that an individual encounters that same antigen the immune system is primed to antigen the immune system is primed to destroy it quickly This is destroy it quickly This is active immunityactive immunity

bull Long-term active immunityLong-term active immunity can be naturally can be naturally acquired by infection or artificially acquired acquired by infection or artificially acquired by vaccines by vaccines

bull Short-term passive immunityShort-term passive immunity can be can be transferred artificially from one individual to transferred artificially from one individual to another via antibody-rich serum another via antibody-rich serum

Active and Passive Acquired Active and Passive Acquired ImmunityImmunity

bull Active immunityActive immunity

ndash Conferred by recovery from infectious diseaseConferred by recovery from infectious disease

ndash Depends on persons own immune systemDepends on persons own immune system

ndash May be acquired artificially with May be acquired artificially with vaccinesvaccines

bull Passive immunityPassive immunity

ndash transferred from person to person through transfer of antibodiestransferred from person to person through transfer of antibodies

ndash Natural instances include antibodies passing across placenta from Natural instances include antibodies passing across placenta from mother to fetus (provides temporary protection) or through the mother to fetus (provides temporary protection) or through the milkmilk

ndash Transferred artificially Eg antibody injections for rabies anti Transferred artificially Eg antibody injections for rabies anti rhesus factor snake venom botulinun toxinrhesus factor snake venom botulinun toxin

bull Lymphatic vessels are responsible for flow of lymph Lymphatic vessels are responsible for flow of lymph within the lymphoid system within the lymphoid system

bull Plasma constantly leaks out of capillaries to deliver Plasma constantly leaks out of capillaries to deliver oxygen and nutrients to cells of the surrounding oxygen and nutrients to cells of the surrounding tissue Once in the tissue the plasma is now called tissue Once in the tissue the plasma is now called tissue fluidtissue fluid

bull While most of this tissue fluid re-enters capillaries While most of this tissue fluid re-enters capillaries and is returned directly to the bloodstream some and is returned directly to the bloodstream some fluid enters lymph vessels as fluid enters lymph vessels as lymph lymph

bull LYMPH-LYMPH- flows from the intercellular tissue spaces flows from the intercellular tissue spaces into lymphatic capillaries and then into a series of into lymphatic capillaries and then into a series of larger collecting vessels called larger collecting vessels called lymphatic vesselslymphatic vessels Lymphatic vessels converge into Lymphatic vessels converge into the thoracic ductthe thoracic duct which returns the fluid to the circulatory system by which returns the fluid to the circulatory system by dumping into the left dumping into the left subclavian vein subclavian vein

Thoracicduct

Overview of blood and lymph system and how Overview of blood and lymph system and how leukocytes travel from one system to anotherleukocytes travel from one system to another

Site of exchange between theblood and lymph systems

Lymph carrying antibodiesand immune cells collect in thoracic duct where the lymph empties back into the blood circulatory system

Immune cells travel back and forth from Immune cells travel back and forth from the blood and lymph circulatory systems the blood and lymph circulatory systems and interact with extra-vascular tissues and interact with extra-vascular tissues

in the process--in the process--extravasationextravasation

muscle

Lymphatic vessels Lymphatic vessels

The organs of the The organs of the immune system immune system

Kinds of lymphoid Kinds of lymphoid OrgansOrgans

Primarycentral lymphoid organsPrimarycentral lymphoid organs ndash bone marrow bone marrow ndash thymus thymus

Secondary peripheral lymphoid tissueSecondary peripheral lymphoid tissuendash lymph nodes lymph nodes ndash spleenspleenndash mucosa-associated lymphoid tissuemucosa-associated lymphoid tissue

Kinds of Lymphoid Organs Kinds of Lymphoid Organs The Lymphoid

Organs

Primary or Central organs

Secondary or Peripheral organs

1Bone marrow2Thymus gland3Bursa of fabricius

1Lymp nodes 2Spleen

3Diffuse lymphoid tissues

bull The The bone marrowbone marrow and the and the thymusthymus constitute constitute the primary lymphoid organsthe primary lymphoid organs

bull Both Both B-lymphocytesB-lymphocytes and and T-lymphocytesT-lymphocytes are are produced from stem cells in the bone produced from stem cells in the bone marrow marrow B-lymphocytes mature in the B-lymphocytes mature in the bone marrow while T-lymphocytes bone marrow while T-lymphocytes migrate to the thymus and mature migrate to the thymus and mature therethere

bull After maturation both B-lymphocytes and T-After maturation both B-lymphocytes and T-lymphocytes circulate through and lymphocytes circulate through and accumulate in accumulate in secondary lymphoid organssecondary lymphoid organs

bull The secondary lymphoid organs include lymph nodes The secondary lymphoid organs include lymph nodes and the spleen as well as lymphoid tissues and the spleen as well as lymphoid tissues

bull The lymphoid tissues include The lymphoid tissues include the tonsils the the tonsils the appendix the Peyers patchesappendix the Peyers patches in the lining of the in the lining of the small intestines (small intestines (gut-associated lymphoid tissue or gut-associated lymphoid tissue or GALTGALT) )

bull The lymphoid tissue found beneath the mucous The lymphoid tissue found beneath the mucous membranes of the bronchi (membranes of the bronchi (bronchial-associated bronchial-associated lymphoid tissue or BALTlymphoid tissue or BALT) )

bull The lymphatic tissue found in the mucous The lymphatic tissue found in the mucous membranes (membranes (mucosa-associated lymphoid tissue or mucosa-associated lymphoid tissue or MALTMALT))

bull The lymphatic tissue found beneath the skin (The lymphatic tissue found beneath the skin (skin-skin-associated lymphoid tissue or SALTassociated lymphoid tissue or SALT) )

Primary and SecondaryPrimary and Secondary Lymphoid organs Lymphoid organs

Primarycentral lymphoid Primarycentral lymphoid organs organs

BONE MARROWBONE MARROW is a central organ is a central organ where all the immune cells are where all the immune cells are born and only B cells mature born and only B cells mature (process termed as (process termed as B B lymphopoiesis) lymphopoiesis)

THYMUSTHYMUS is the other central organ is the other central organ in which T cells mature (in which T cells mature (T T lymphopoiesislymphopoiesis) )

The bone marrowThe bone marrow

Bone marrow is a spongy tissue found Bone marrow is a spongy tissue found within boneswithin bonesAll blood cells are produced within the bone All blood cells are produced within the bone marrowmarrowThe bone marrow of an adult produce about The bone marrow of an adult produce about three million red blood cells and 120000 three million red blood cells and 120000 white blood cells every second white blood cells every second All these cells originate from a small All these cells originate from a small population of stem cells which may be as population of stem cells which may be as few as one in a million of the bone marrow few as one in a million of the bone marrow cells cells

ThymuThymuss

bullThe thymus is an organ located in the The thymus is an organ located in the upper chestupper chest bullImmature lymphocytes leave the bone Immature lymphocytes leave the bone marrow and find their way to the thymus marrow and find their way to the thymus where they are ldquoeducatedrdquo to become where they are ldquoeducatedrdquo to become mature T-lymphocytesmature T-lymphocytes

ThymusThymusFlat bilobed organ situated above the heart Flat bilobed organ situated above the heart

and below the thyroid glandand below the thyroid gland Each lobe is surrounded by a capsule and is Each lobe is surrounded by a capsule and is

divided into lobules divided into lobules The lobules are separated from each other by The lobules are separated from each other by

strands of connective tissue called strands of connective tissue called trabeculaetrabeculae

Each lobule is organized into two Each lobule is organized into two compartments the compartments the cortex cortex (outer (outer compartment) the compartment) the medullamedulla (inner (inner compartment) compartment)

bull Cortex and Medulla are both crisscrossed by Cortex and Medulla are both crisscrossed by a a network of stromal cellsnetwork of stromal cells composed of composed of

bull loosely packed thymic epithelial cells loosely packed thymic epithelial cells bull interdigitating dendritic cells interdigitating dendritic cells bull macrophages macrophages

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 13: Functional organization of the Immune System

Three Lines of DefenseThree Lines of Defense

1st Line ndash barriers at portals of entry1st Line ndash barriers at portals of entry10486981048698primarily inborn and nonspecificprimarily inborn and nonspecific

2nd Line ndash protective cells and chemicals2nd Line ndash protective cells and chemicals10486981048698come into play when barriers are breachedcome into play when barriers are breached10486981048698primarily inborn and nonspecificprimarily inborn and nonspecific

3rd Line ndash antibodies and cytotoxic cells3rd Line ndash antibodies and cytotoxic cells10486981048698provides long-term immunity after provides long-term immunity after encountersencounters10486981048698primarily acquired and specificprimarily acquired and specific

Lines of defenseLines of defensebull 11stst lines of defense lines of defense are the physical barriers which include are the physical barriers which include

the skin urine tears ciliary elevator mucosal membrane etcthe skin urine tears ciliary elevator mucosal membrane etc

bull 22ndnd lines of defense lines of defense are the macrophage system are the macrophage system complement fever interferon and inflammation complement fever interferon and inflammation

bull 33rdrd lines of defense lines of defense aare the specific system also known re the specific system also known as acquired or adaptive immunity The specific system consists of B cells (humoral) and T cells (cell-mediated)

Physical and Chemical Physical and Chemical DefensesDefenses

First line of defense-1First line of defense-1

bull The first line of defense are The first line of defense are barrier barrier tissuestissues such as the skin that stop the such as the skin that stop the entry of pathogens into our bodiesentry of pathogens into our bodies

bull If these barrier layers are If these barrier layers are penetrated cells like penetrated cells like macrophages macrophages and neutrophilsand neutrophils engulf foreign engulf foreign organisms and kill them without the organisms and kill them without the need for antibodies need for antibodies

First Line of Defense-2First Line of Defense-2

bull SkinSkin provides an almost impenetrable provides an almost impenetrable biological barrier biological barrier

bull Lysozyme Lysozyme is an enzyme found in tears is an enzyme found in tears and saliva that and saliva that can break down foreign can break down foreign agents agents

bull The clotting of blood near open wounds The clotting of blood near open wounds prevents an open space for antigensprevents an open space for antigens

bull Mucus and cilia found in the nose and Mucus and cilia found in the nose and throat can catch foreign agents then throat can catch foreign agents then sweep them outside via sweep them outside via coughing coughing sneezing and vomiting sneezing and vomiting

bull The cell wall of plants consists of The cell wall of plants consists of fibrous fibrous proteinsproteins which provide a barrier to which provide a barrier to potential parasites (antigens) potential parasites (antigens)

A second line of defense-1A second line of defense-1

bull A second line of defense is the specific or A second line of defense is the specific or adaptive adaptive immune systemimmune system which may take days to respond which may take days to respond to a primary invasion to a primary invasion

bull The The production of antibodies and cell-mediated production of antibodies and cell-mediated responsesresponses may occur in which specific cells may occur in which specific cells recognize foreign pathogens and destroy themrecognize foreign pathogens and destroy them

bull The response is often more rapid because of the The response is often more rapid because of the activation of memory B and T cellsactivation of memory B and T cells

bull cells of the immune system interact with one cells of the immune system interact with one another by a variety of another by a variety of signal moleculessignal molecules

bull These signals may be proteins such as These signals may be proteins such as lymphokines cytokines and chemokineslymphokines cytokines and chemokines which which stimulate cells of the immune system stimulate cells of the immune system

Second Line of Defense-2Second Line of Defense-2

bull Second lines of defense deal with Second lines of defense deal with antigens that have bypassed the first antigens that have bypassed the first lines of defense lines of defense

bull InterferonsInterferons are a family of proteins that are a family of proteins that are released by a cell that is under are released by a cell that is under attack by an antigen attack by an antigen

bull One method of attacking antigens is by One method of attacking antigens is by phagocytosisphagocytosis where the contents of where the contents of the antigen are broken down by the antigen are broken down by molecules called phagocytesmolecules called phagocytes

Adaptive immunityAdaptive immunity

bull The The second levelsecond level of defence increases in of defence increases in strength and effectiveness with each strength and effectiveness with each encounter The foreign agent is recognised encounter The foreign agent is recognised in a specific manner and the immune system in a specific manner and the immune system acquires memory towards it acquires memory towards it

bull The first encounter with an antigen is The first encounter with an antigen is known as known as the primary responsethe primary response Re- Re-encounter with the same antigen causes a encounter with the same antigen causes a secondary responsesecondary response that is more rapid and that is more rapid and powerfulpowerful

Adaptive immunityAdaptive immunitybull As response produce antibodies to specific As response produce antibodies to specific

infectionsinfections

Some featuresSome features

ndash ndash MemoryMemorybull Each successive encounter with the same Each successive encounter with the same

pathogen improve the responsepathogen improve the response

ndash ndash Clonal selectionClonal selectionbull Select the best and matured immune cells Select the best and matured immune cells

to defend the organism against infectionsto defend the organism against infections

bull Whenever T cells and B cells are activated Whenever T cells and B cells are activated some become some become memory cellsmemory cells The next time The next time that an individual encounters that same that an individual encounters that same antigen the immune system is primed to antigen the immune system is primed to destroy it quickly This is destroy it quickly This is active immunityactive immunity

bull Long-term active immunityLong-term active immunity can be naturally can be naturally acquired by infection or artificially acquired acquired by infection or artificially acquired by vaccines by vaccines

bull Short-term passive immunityShort-term passive immunity can be can be transferred artificially from one individual to transferred artificially from one individual to another via antibody-rich serum another via antibody-rich serum

Active and Passive Acquired Active and Passive Acquired ImmunityImmunity

bull Active immunityActive immunity

ndash Conferred by recovery from infectious diseaseConferred by recovery from infectious disease

ndash Depends on persons own immune systemDepends on persons own immune system

ndash May be acquired artificially with May be acquired artificially with vaccinesvaccines

bull Passive immunityPassive immunity

ndash transferred from person to person through transfer of antibodiestransferred from person to person through transfer of antibodies

ndash Natural instances include antibodies passing across placenta from Natural instances include antibodies passing across placenta from mother to fetus (provides temporary protection) or through the mother to fetus (provides temporary protection) or through the milkmilk

ndash Transferred artificially Eg antibody injections for rabies anti Transferred artificially Eg antibody injections for rabies anti rhesus factor snake venom botulinun toxinrhesus factor snake venom botulinun toxin

bull Lymphatic vessels are responsible for flow of lymph Lymphatic vessels are responsible for flow of lymph within the lymphoid system within the lymphoid system

bull Plasma constantly leaks out of capillaries to deliver Plasma constantly leaks out of capillaries to deliver oxygen and nutrients to cells of the surrounding oxygen and nutrients to cells of the surrounding tissue Once in the tissue the plasma is now called tissue Once in the tissue the plasma is now called tissue fluidtissue fluid

bull While most of this tissue fluid re-enters capillaries While most of this tissue fluid re-enters capillaries and is returned directly to the bloodstream some and is returned directly to the bloodstream some fluid enters lymph vessels as fluid enters lymph vessels as lymph lymph

bull LYMPH-LYMPH- flows from the intercellular tissue spaces flows from the intercellular tissue spaces into lymphatic capillaries and then into a series of into lymphatic capillaries and then into a series of larger collecting vessels called larger collecting vessels called lymphatic vesselslymphatic vessels Lymphatic vessels converge into Lymphatic vessels converge into the thoracic ductthe thoracic duct which returns the fluid to the circulatory system by which returns the fluid to the circulatory system by dumping into the left dumping into the left subclavian vein subclavian vein

Thoracicduct

Overview of blood and lymph system and how Overview of blood and lymph system and how leukocytes travel from one system to anotherleukocytes travel from one system to another

Site of exchange between theblood and lymph systems

Lymph carrying antibodiesand immune cells collect in thoracic duct where the lymph empties back into the blood circulatory system

Immune cells travel back and forth from Immune cells travel back and forth from the blood and lymph circulatory systems the blood and lymph circulatory systems and interact with extra-vascular tissues and interact with extra-vascular tissues

in the process--in the process--extravasationextravasation

muscle

Lymphatic vessels Lymphatic vessels

The organs of the The organs of the immune system immune system

Kinds of lymphoid Kinds of lymphoid OrgansOrgans

Primarycentral lymphoid organsPrimarycentral lymphoid organs ndash bone marrow bone marrow ndash thymus thymus

Secondary peripheral lymphoid tissueSecondary peripheral lymphoid tissuendash lymph nodes lymph nodes ndash spleenspleenndash mucosa-associated lymphoid tissuemucosa-associated lymphoid tissue

Kinds of Lymphoid Organs Kinds of Lymphoid Organs The Lymphoid

Organs

Primary or Central organs

Secondary or Peripheral organs

1Bone marrow2Thymus gland3Bursa of fabricius

1Lymp nodes 2Spleen

3Diffuse lymphoid tissues

bull The The bone marrowbone marrow and the and the thymusthymus constitute constitute the primary lymphoid organsthe primary lymphoid organs

bull Both Both B-lymphocytesB-lymphocytes and and T-lymphocytesT-lymphocytes are are produced from stem cells in the bone produced from stem cells in the bone marrow marrow B-lymphocytes mature in the B-lymphocytes mature in the bone marrow while T-lymphocytes bone marrow while T-lymphocytes migrate to the thymus and mature migrate to the thymus and mature therethere

bull After maturation both B-lymphocytes and T-After maturation both B-lymphocytes and T-lymphocytes circulate through and lymphocytes circulate through and accumulate in accumulate in secondary lymphoid organssecondary lymphoid organs

bull The secondary lymphoid organs include lymph nodes The secondary lymphoid organs include lymph nodes and the spleen as well as lymphoid tissues and the spleen as well as lymphoid tissues

bull The lymphoid tissues include The lymphoid tissues include the tonsils the the tonsils the appendix the Peyers patchesappendix the Peyers patches in the lining of the in the lining of the small intestines (small intestines (gut-associated lymphoid tissue or gut-associated lymphoid tissue or GALTGALT) )

bull The lymphoid tissue found beneath the mucous The lymphoid tissue found beneath the mucous membranes of the bronchi (membranes of the bronchi (bronchial-associated bronchial-associated lymphoid tissue or BALTlymphoid tissue or BALT) )

bull The lymphatic tissue found in the mucous The lymphatic tissue found in the mucous membranes (membranes (mucosa-associated lymphoid tissue or mucosa-associated lymphoid tissue or MALTMALT))

bull The lymphatic tissue found beneath the skin (The lymphatic tissue found beneath the skin (skin-skin-associated lymphoid tissue or SALTassociated lymphoid tissue or SALT) )

Primary and SecondaryPrimary and Secondary Lymphoid organs Lymphoid organs

Primarycentral lymphoid Primarycentral lymphoid organs organs

BONE MARROWBONE MARROW is a central organ is a central organ where all the immune cells are where all the immune cells are born and only B cells mature born and only B cells mature (process termed as (process termed as B B lymphopoiesis) lymphopoiesis)

THYMUSTHYMUS is the other central organ is the other central organ in which T cells mature (in which T cells mature (T T lymphopoiesislymphopoiesis) )

The bone marrowThe bone marrow

Bone marrow is a spongy tissue found Bone marrow is a spongy tissue found within boneswithin bonesAll blood cells are produced within the bone All blood cells are produced within the bone marrowmarrowThe bone marrow of an adult produce about The bone marrow of an adult produce about three million red blood cells and 120000 three million red blood cells and 120000 white blood cells every second white blood cells every second All these cells originate from a small All these cells originate from a small population of stem cells which may be as population of stem cells which may be as few as one in a million of the bone marrow few as one in a million of the bone marrow cells cells

ThymuThymuss

bullThe thymus is an organ located in the The thymus is an organ located in the upper chestupper chest bullImmature lymphocytes leave the bone Immature lymphocytes leave the bone marrow and find their way to the thymus marrow and find their way to the thymus where they are ldquoeducatedrdquo to become where they are ldquoeducatedrdquo to become mature T-lymphocytesmature T-lymphocytes

ThymusThymusFlat bilobed organ situated above the heart Flat bilobed organ situated above the heart

and below the thyroid glandand below the thyroid gland Each lobe is surrounded by a capsule and is Each lobe is surrounded by a capsule and is

divided into lobules divided into lobules The lobules are separated from each other by The lobules are separated from each other by

strands of connective tissue called strands of connective tissue called trabeculaetrabeculae

Each lobule is organized into two Each lobule is organized into two compartments the compartments the cortex cortex (outer (outer compartment) the compartment) the medullamedulla (inner (inner compartment) compartment)

bull Cortex and Medulla are both crisscrossed by Cortex and Medulla are both crisscrossed by a a network of stromal cellsnetwork of stromal cells composed of composed of

bull loosely packed thymic epithelial cells loosely packed thymic epithelial cells bull interdigitating dendritic cells interdigitating dendritic cells bull macrophages macrophages

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 14: Functional organization of the Immune System

Lines of defenseLines of defensebull 11stst lines of defense lines of defense are the physical barriers which include are the physical barriers which include

the skin urine tears ciliary elevator mucosal membrane etcthe skin urine tears ciliary elevator mucosal membrane etc

bull 22ndnd lines of defense lines of defense are the macrophage system are the macrophage system complement fever interferon and inflammation complement fever interferon and inflammation

bull 33rdrd lines of defense lines of defense aare the specific system also known re the specific system also known as acquired or adaptive immunity The specific system consists of B cells (humoral) and T cells (cell-mediated)

Physical and Chemical Physical and Chemical DefensesDefenses

First line of defense-1First line of defense-1

bull The first line of defense are The first line of defense are barrier barrier tissuestissues such as the skin that stop the such as the skin that stop the entry of pathogens into our bodiesentry of pathogens into our bodies

bull If these barrier layers are If these barrier layers are penetrated cells like penetrated cells like macrophages macrophages and neutrophilsand neutrophils engulf foreign engulf foreign organisms and kill them without the organisms and kill them without the need for antibodies need for antibodies

First Line of Defense-2First Line of Defense-2

bull SkinSkin provides an almost impenetrable provides an almost impenetrable biological barrier biological barrier

bull Lysozyme Lysozyme is an enzyme found in tears is an enzyme found in tears and saliva that and saliva that can break down foreign can break down foreign agents agents

bull The clotting of blood near open wounds The clotting of blood near open wounds prevents an open space for antigensprevents an open space for antigens

bull Mucus and cilia found in the nose and Mucus and cilia found in the nose and throat can catch foreign agents then throat can catch foreign agents then sweep them outside via sweep them outside via coughing coughing sneezing and vomiting sneezing and vomiting

bull The cell wall of plants consists of The cell wall of plants consists of fibrous fibrous proteinsproteins which provide a barrier to which provide a barrier to potential parasites (antigens) potential parasites (antigens)

A second line of defense-1A second line of defense-1

bull A second line of defense is the specific or A second line of defense is the specific or adaptive adaptive immune systemimmune system which may take days to respond which may take days to respond to a primary invasion to a primary invasion

bull The The production of antibodies and cell-mediated production of antibodies and cell-mediated responsesresponses may occur in which specific cells may occur in which specific cells recognize foreign pathogens and destroy themrecognize foreign pathogens and destroy them

bull The response is often more rapid because of the The response is often more rapid because of the activation of memory B and T cellsactivation of memory B and T cells

bull cells of the immune system interact with one cells of the immune system interact with one another by a variety of another by a variety of signal moleculessignal molecules

bull These signals may be proteins such as These signals may be proteins such as lymphokines cytokines and chemokineslymphokines cytokines and chemokines which which stimulate cells of the immune system stimulate cells of the immune system

Second Line of Defense-2Second Line of Defense-2

bull Second lines of defense deal with Second lines of defense deal with antigens that have bypassed the first antigens that have bypassed the first lines of defense lines of defense

bull InterferonsInterferons are a family of proteins that are a family of proteins that are released by a cell that is under are released by a cell that is under attack by an antigen attack by an antigen

bull One method of attacking antigens is by One method of attacking antigens is by phagocytosisphagocytosis where the contents of where the contents of the antigen are broken down by the antigen are broken down by molecules called phagocytesmolecules called phagocytes

Adaptive immunityAdaptive immunity

bull The The second levelsecond level of defence increases in of defence increases in strength and effectiveness with each strength and effectiveness with each encounter The foreign agent is recognised encounter The foreign agent is recognised in a specific manner and the immune system in a specific manner and the immune system acquires memory towards it acquires memory towards it

bull The first encounter with an antigen is The first encounter with an antigen is known as known as the primary responsethe primary response Re- Re-encounter with the same antigen causes a encounter with the same antigen causes a secondary responsesecondary response that is more rapid and that is more rapid and powerfulpowerful

Adaptive immunityAdaptive immunitybull As response produce antibodies to specific As response produce antibodies to specific

infectionsinfections

Some featuresSome features

ndash ndash MemoryMemorybull Each successive encounter with the same Each successive encounter with the same

pathogen improve the responsepathogen improve the response

ndash ndash Clonal selectionClonal selectionbull Select the best and matured immune cells Select the best and matured immune cells

to defend the organism against infectionsto defend the organism against infections

bull Whenever T cells and B cells are activated Whenever T cells and B cells are activated some become some become memory cellsmemory cells The next time The next time that an individual encounters that same that an individual encounters that same antigen the immune system is primed to antigen the immune system is primed to destroy it quickly This is destroy it quickly This is active immunityactive immunity

bull Long-term active immunityLong-term active immunity can be naturally can be naturally acquired by infection or artificially acquired acquired by infection or artificially acquired by vaccines by vaccines

bull Short-term passive immunityShort-term passive immunity can be can be transferred artificially from one individual to transferred artificially from one individual to another via antibody-rich serum another via antibody-rich serum

Active and Passive Acquired Active and Passive Acquired ImmunityImmunity

bull Active immunityActive immunity

ndash Conferred by recovery from infectious diseaseConferred by recovery from infectious disease

ndash Depends on persons own immune systemDepends on persons own immune system

ndash May be acquired artificially with May be acquired artificially with vaccinesvaccines

bull Passive immunityPassive immunity

ndash transferred from person to person through transfer of antibodiestransferred from person to person through transfer of antibodies

ndash Natural instances include antibodies passing across placenta from Natural instances include antibodies passing across placenta from mother to fetus (provides temporary protection) or through the mother to fetus (provides temporary protection) or through the milkmilk

ndash Transferred artificially Eg antibody injections for rabies anti Transferred artificially Eg antibody injections for rabies anti rhesus factor snake venom botulinun toxinrhesus factor snake venom botulinun toxin

bull Lymphatic vessels are responsible for flow of lymph Lymphatic vessels are responsible for flow of lymph within the lymphoid system within the lymphoid system

bull Plasma constantly leaks out of capillaries to deliver Plasma constantly leaks out of capillaries to deliver oxygen and nutrients to cells of the surrounding oxygen and nutrients to cells of the surrounding tissue Once in the tissue the plasma is now called tissue Once in the tissue the plasma is now called tissue fluidtissue fluid

bull While most of this tissue fluid re-enters capillaries While most of this tissue fluid re-enters capillaries and is returned directly to the bloodstream some and is returned directly to the bloodstream some fluid enters lymph vessels as fluid enters lymph vessels as lymph lymph

bull LYMPH-LYMPH- flows from the intercellular tissue spaces flows from the intercellular tissue spaces into lymphatic capillaries and then into a series of into lymphatic capillaries and then into a series of larger collecting vessels called larger collecting vessels called lymphatic vesselslymphatic vessels Lymphatic vessels converge into Lymphatic vessels converge into the thoracic ductthe thoracic duct which returns the fluid to the circulatory system by which returns the fluid to the circulatory system by dumping into the left dumping into the left subclavian vein subclavian vein

Thoracicduct

Overview of blood and lymph system and how Overview of blood and lymph system and how leukocytes travel from one system to anotherleukocytes travel from one system to another

Site of exchange between theblood and lymph systems

Lymph carrying antibodiesand immune cells collect in thoracic duct where the lymph empties back into the blood circulatory system

Immune cells travel back and forth from Immune cells travel back and forth from the blood and lymph circulatory systems the blood and lymph circulatory systems and interact with extra-vascular tissues and interact with extra-vascular tissues

in the process--in the process--extravasationextravasation

muscle

Lymphatic vessels Lymphatic vessels

The organs of the The organs of the immune system immune system

Kinds of lymphoid Kinds of lymphoid OrgansOrgans

Primarycentral lymphoid organsPrimarycentral lymphoid organs ndash bone marrow bone marrow ndash thymus thymus

Secondary peripheral lymphoid tissueSecondary peripheral lymphoid tissuendash lymph nodes lymph nodes ndash spleenspleenndash mucosa-associated lymphoid tissuemucosa-associated lymphoid tissue

Kinds of Lymphoid Organs Kinds of Lymphoid Organs The Lymphoid

Organs

Primary or Central organs

Secondary or Peripheral organs

1Bone marrow2Thymus gland3Bursa of fabricius

1Lymp nodes 2Spleen

3Diffuse lymphoid tissues

bull The The bone marrowbone marrow and the and the thymusthymus constitute constitute the primary lymphoid organsthe primary lymphoid organs

bull Both Both B-lymphocytesB-lymphocytes and and T-lymphocytesT-lymphocytes are are produced from stem cells in the bone produced from stem cells in the bone marrow marrow B-lymphocytes mature in the B-lymphocytes mature in the bone marrow while T-lymphocytes bone marrow while T-lymphocytes migrate to the thymus and mature migrate to the thymus and mature therethere

bull After maturation both B-lymphocytes and T-After maturation both B-lymphocytes and T-lymphocytes circulate through and lymphocytes circulate through and accumulate in accumulate in secondary lymphoid organssecondary lymphoid organs

bull The secondary lymphoid organs include lymph nodes The secondary lymphoid organs include lymph nodes and the spleen as well as lymphoid tissues and the spleen as well as lymphoid tissues

bull The lymphoid tissues include The lymphoid tissues include the tonsils the the tonsils the appendix the Peyers patchesappendix the Peyers patches in the lining of the in the lining of the small intestines (small intestines (gut-associated lymphoid tissue or gut-associated lymphoid tissue or GALTGALT) )

bull The lymphoid tissue found beneath the mucous The lymphoid tissue found beneath the mucous membranes of the bronchi (membranes of the bronchi (bronchial-associated bronchial-associated lymphoid tissue or BALTlymphoid tissue or BALT) )

bull The lymphatic tissue found in the mucous The lymphatic tissue found in the mucous membranes (membranes (mucosa-associated lymphoid tissue or mucosa-associated lymphoid tissue or MALTMALT))

bull The lymphatic tissue found beneath the skin (The lymphatic tissue found beneath the skin (skin-skin-associated lymphoid tissue or SALTassociated lymphoid tissue or SALT) )

Primary and SecondaryPrimary and Secondary Lymphoid organs Lymphoid organs

Primarycentral lymphoid Primarycentral lymphoid organs organs

BONE MARROWBONE MARROW is a central organ is a central organ where all the immune cells are where all the immune cells are born and only B cells mature born and only B cells mature (process termed as (process termed as B B lymphopoiesis) lymphopoiesis)

THYMUSTHYMUS is the other central organ is the other central organ in which T cells mature (in which T cells mature (T T lymphopoiesislymphopoiesis) )

The bone marrowThe bone marrow

Bone marrow is a spongy tissue found Bone marrow is a spongy tissue found within boneswithin bonesAll blood cells are produced within the bone All blood cells are produced within the bone marrowmarrowThe bone marrow of an adult produce about The bone marrow of an adult produce about three million red blood cells and 120000 three million red blood cells and 120000 white blood cells every second white blood cells every second All these cells originate from a small All these cells originate from a small population of stem cells which may be as population of stem cells which may be as few as one in a million of the bone marrow few as one in a million of the bone marrow cells cells

ThymuThymuss

bullThe thymus is an organ located in the The thymus is an organ located in the upper chestupper chest bullImmature lymphocytes leave the bone Immature lymphocytes leave the bone marrow and find their way to the thymus marrow and find their way to the thymus where they are ldquoeducatedrdquo to become where they are ldquoeducatedrdquo to become mature T-lymphocytesmature T-lymphocytes

ThymusThymusFlat bilobed organ situated above the heart Flat bilobed organ situated above the heart

and below the thyroid glandand below the thyroid gland Each lobe is surrounded by a capsule and is Each lobe is surrounded by a capsule and is

divided into lobules divided into lobules The lobules are separated from each other by The lobules are separated from each other by

strands of connective tissue called strands of connective tissue called trabeculaetrabeculae

Each lobule is organized into two Each lobule is organized into two compartments the compartments the cortex cortex (outer (outer compartment) the compartment) the medullamedulla (inner (inner compartment) compartment)

bull Cortex and Medulla are both crisscrossed by Cortex and Medulla are both crisscrossed by a a network of stromal cellsnetwork of stromal cells composed of composed of

bull loosely packed thymic epithelial cells loosely packed thymic epithelial cells bull interdigitating dendritic cells interdigitating dendritic cells bull macrophages macrophages

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 15: Functional organization of the Immune System

Physical and Chemical Physical and Chemical DefensesDefenses

First line of defense-1First line of defense-1

bull The first line of defense are The first line of defense are barrier barrier tissuestissues such as the skin that stop the such as the skin that stop the entry of pathogens into our bodiesentry of pathogens into our bodies

bull If these barrier layers are If these barrier layers are penetrated cells like penetrated cells like macrophages macrophages and neutrophilsand neutrophils engulf foreign engulf foreign organisms and kill them without the organisms and kill them without the need for antibodies need for antibodies

First Line of Defense-2First Line of Defense-2

bull SkinSkin provides an almost impenetrable provides an almost impenetrable biological barrier biological barrier

bull Lysozyme Lysozyme is an enzyme found in tears is an enzyme found in tears and saliva that and saliva that can break down foreign can break down foreign agents agents

bull The clotting of blood near open wounds The clotting of blood near open wounds prevents an open space for antigensprevents an open space for antigens

bull Mucus and cilia found in the nose and Mucus and cilia found in the nose and throat can catch foreign agents then throat can catch foreign agents then sweep them outside via sweep them outside via coughing coughing sneezing and vomiting sneezing and vomiting

bull The cell wall of plants consists of The cell wall of plants consists of fibrous fibrous proteinsproteins which provide a barrier to which provide a barrier to potential parasites (antigens) potential parasites (antigens)

A second line of defense-1A second line of defense-1

bull A second line of defense is the specific or A second line of defense is the specific or adaptive adaptive immune systemimmune system which may take days to respond which may take days to respond to a primary invasion to a primary invasion

bull The The production of antibodies and cell-mediated production of antibodies and cell-mediated responsesresponses may occur in which specific cells may occur in which specific cells recognize foreign pathogens and destroy themrecognize foreign pathogens and destroy them

bull The response is often more rapid because of the The response is often more rapid because of the activation of memory B and T cellsactivation of memory B and T cells

bull cells of the immune system interact with one cells of the immune system interact with one another by a variety of another by a variety of signal moleculessignal molecules

bull These signals may be proteins such as These signals may be proteins such as lymphokines cytokines and chemokineslymphokines cytokines and chemokines which which stimulate cells of the immune system stimulate cells of the immune system

Second Line of Defense-2Second Line of Defense-2

bull Second lines of defense deal with Second lines of defense deal with antigens that have bypassed the first antigens that have bypassed the first lines of defense lines of defense

bull InterferonsInterferons are a family of proteins that are a family of proteins that are released by a cell that is under are released by a cell that is under attack by an antigen attack by an antigen

bull One method of attacking antigens is by One method of attacking antigens is by phagocytosisphagocytosis where the contents of where the contents of the antigen are broken down by the antigen are broken down by molecules called phagocytesmolecules called phagocytes

Adaptive immunityAdaptive immunity

bull The The second levelsecond level of defence increases in of defence increases in strength and effectiveness with each strength and effectiveness with each encounter The foreign agent is recognised encounter The foreign agent is recognised in a specific manner and the immune system in a specific manner and the immune system acquires memory towards it acquires memory towards it

bull The first encounter with an antigen is The first encounter with an antigen is known as known as the primary responsethe primary response Re- Re-encounter with the same antigen causes a encounter with the same antigen causes a secondary responsesecondary response that is more rapid and that is more rapid and powerfulpowerful

Adaptive immunityAdaptive immunitybull As response produce antibodies to specific As response produce antibodies to specific

infectionsinfections

Some featuresSome features

ndash ndash MemoryMemorybull Each successive encounter with the same Each successive encounter with the same

pathogen improve the responsepathogen improve the response

ndash ndash Clonal selectionClonal selectionbull Select the best and matured immune cells Select the best and matured immune cells

to defend the organism against infectionsto defend the organism against infections

bull Whenever T cells and B cells are activated Whenever T cells and B cells are activated some become some become memory cellsmemory cells The next time The next time that an individual encounters that same that an individual encounters that same antigen the immune system is primed to antigen the immune system is primed to destroy it quickly This is destroy it quickly This is active immunityactive immunity

bull Long-term active immunityLong-term active immunity can be naturally can be naturally acquired by infection or artificially acquired acquired by infection or artificially acquired by vaccines by vaccines

bull Short-term passive immunityShort-term passive immunity can be can be transferred artificially from one individual to transferred artificially from one individual to another via antibody-rich serum another via antibody-rich serum

Active and Passive Acquired Active and Passive Acquired ImmunityImmunity

bull Active immunityActive immunity

ndash Conferred by recovery from infectious diseaseConferred by recovery from infectious disease

ndash Depends on persons own immune systemDepends on persons own immune system

ndash May be acquired artificially with May be acquired artificially with vaccinesvaccines

bull Passive immunityPassive immunity

ndash transferred from person to person through transfer of antibodiestransferred from person to person through transfer of antibodies

ndash Natural instances include antibodies passing across placenta from Natural instances include antibodies passing across placenta from mother to fetus (provides temporary protection) or through the mother to fetus (provides temporary protection) or through the milkmilk

ndash Transferred artificially Eg antibody injections for rabies anti Transferred artificially Eg antibody injections for rabies anti rhesus factor snake venom botulinun toxinrhesus factor snake venom botulinun toxin

bull Lymphatic vessels are responsible for flow of lymph Lymphatic vessels are responsible for flow of lymph within the lymphoid system within the lymphoid system

bull Plasma constantly leaks out of capillaries to deliver Plasma constantly leaks out of capillaries to deliver oxygen and nutrients to cells of the surrounding oxygen and nutrients to cells of the surrounding tissue Once in the tissue the plasma is now called tissue Once in the tissue the plasma is now called tissue fluidtissue fluid

bull While most of this tissue fluid re-enters capillaries While most of this tissue fluid re-enters capillaries and is returned directly to the bloodstream some and is returned directly to the bloodstream some fluid enters lymph vessels as fluid enters lymph vessels as lymph lymph

bull LYMPH-LYMPH- flows from the intercellular tissue spaces flows from the intercellular tissue spaces into lymphatic capillaries and then into a series of into lymphatic capillaries and then into a series of larger collecting vessels called larger collecting vessels called lymphatic vesselslymphatic vessels Lymphatic vessels converge into Lymphatic vessels converge into the thoracic ductthe thoracic duct which returns the fluid to the circulatory system by which returns the fluid to the circulatory system by dumping into the left dumping into the left subclavian vein subclavian vein

Thoracicduct

Overview of blood and lymph system and how Overview of blood and lymph system and how leukocytes travel from one system to anotherleukocytes travel from one system to another

Site of exchange between theblood and lymph systems

Lymph carrying antibodiesand immune cells collect in thoracic duct where the lymph empties back into the blood circulatory system

Immune cells travel back and forth from Immune cells travel back and forth from the blood and lymph circulatory systems the blood and lymph circulatory systems and interact with extra-vascular tissues and interact with extra-vascular tissues

in the process--in the process--extravasationextravasation

muscle

Lymphatic vessels Lymphatic vessels

The organs of the The organs of the immune system immune system

Kinds of lymphoid Kinds of lymphoid OrgansOrgans

Primarycentral lymphoid organsPrimarycentral lymphoid organs ndash bone marrow bone marrow ndash thymus thymus

Secondary peripheral lymphoid tissueSecondary peripheral lymphoid tissuendash lymph nodes lymph nodes ndash spleenspleenndash mucosa-associated lymphoid tissuemucosa-associated lymphoid tissue

Kinds of Lymphoid Organs Kinds of Lymphoid Organs The Lymphoid

Organs

Primary or Central organs

Secondary or Peripheral organs

1Bone marrow2Thymus gland3Bursa of fabricius

1Lymp nodes 2Spleen

3Diffuse lymphoid tissues

bull The The bone marrowbone marrow and the and the thymusthymus constitute constitute the primary lymphoid organsthe primary lymphoid organs

bull Both Both B-lymphocytesB-lymphocytes and and T-lymphocytesT-lymphocytes are are produced from stem cells in the bone produced from stem cells in the bone marrow marrow B-lymphocytes mature in the B-lymphocytes mature in the bone marrow while T-lymphocytes bone marrow while T-lymphocytes migrate to the thymus and mature migrate to the thymus and mature therethere

bull After maturation both B-lymphocytes and T-After maturation both B-lymphocytes and T-lymphocytes circulate through and lymphocytes circulate through and accumulate in accumulate in secondary lymphoid organssecondary lymphoid organs

bull The secondary lymphoid organs include lymph nodes The secondary lymphoid organs include lymph nodes and the spleen as well as lymphoid tissues and the spleen as well as lymphoid tissues

bull The lymphoid tissues include The lymphoid tissues include the tonsils the the tonsils the appendix the Peyers patchesappendix the Peyers patches in the lining of the in the lining of the small intestines (small intestines (gut-associated lymphoid tissue or gut-associated lymphoid tissue or GALTGALT) )

bull The lymphoid tissue found beneath the mucous The lymphoid tissue found beneath the mucous membranes of the bronchi (membranes of the bronchi (bronchial-associated bronchial-associated lymphoid tissue or BALTlymphoid tissue or BALT) )

bull The lymphatic tissue found in the mucous The lymphatic tissue found in the mucous membranes (membranes (mucosa-associated lymphoid tissue or mucosa-associated lymphoid tissue or MALTMALT))

bull The lymphatic tissue found beneath the skin (The lymphatic tissue found beneath the skin (skin-skin-associated lymphoid tissue or SALTassociated lymphoid tissue or SALT) )

Primary and SecondaryPrimary and Secondary Lymphoid organs Lymphoid organs

Primarycentral lymphoid Primarycentral lymphoid organs organs

BONE MARROWBONE MARROW is a central organ is a central organ where all the immune cells are where all the immune cells are born and only B cells mature born and only B cells mature (process termed as (process termed as B B lymphopoiesis) lymphopoiesis)

THYMUSTHYMUS is the other central organ is the other central organ in which T cells mature (in which T cells mature (T T lymphopoiesislymphopoiesis) )

The bone marrowThe bone marrow

Bone marrow is a spongy tissue found Bone marrow is a spongy tissue found within boneswithin bonesAll blood cells are produced within the bone All blood cells are produced within the bone marrowmarrowThe bone marrow of an adult produce about The bone marrow of an adult produce about three million red blood cells and 120000 three million red blood cells and 120000 white blood cells every second white blood cells every second All these cells originate from a small All these cells originate from a small population of stem cells which may be as population of stem cells which may be as few as one in a million of the bone marrow few as one in a million of the bone marrow cells cells

ThymuThymuss

bullThe thymus is an organ located in the The thymus is an organ located in the upper chestupper chest bullImmature lymphocytes leave the bone Immature lymphocytes leave the bone marrow and find their way to the thymus marrow and find their way to the thymus where they are ldquoeducatedrdquo to become where they are ldquoeducatedrdquo to become mature T-lymphocytesmature T-lymphocytes

ThymusThymusFlat bilobed organ situated above the heart Flat bilobed organ situated above the heart

and below the thyroid glandand below the thyroid gland Each lobe is surrounded by a capsule and is Each lobe is surrounded by a capsule and is

divided into lobules divided into lobules The lobules are separated from each other by The lobules are separated from each other by

strands of connective tissue called strands of connective tissue called trabeculaetrabeculae

Each lobule is organized into two Each lobule is organized into two compartments the compartments the cortex cortex (outer (outer compartment) the compartment) the medullamedulla (inner (inner compartment) compartment)

bull Cortex and Medulla are both crisscrossed by Cortex and Medulla are both crisscrossed by a a network of stromal cellsnetwork of stromal cells composed of composed of

bull loosely packed thymic epithelial cells loosely packed thymic epithelial cells bull interdigitating dendritic cells interdigitating dendritic cells bull macrophages macrophages

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 16: Functional organization of the Immune System

First line of defense-1First line of defense-1

bull The first line of defense are The first line of defense are barrier barrier tissuestissues such as the skin that stop the such as the skin that stop the entry of pathogens into our bodiesentry of pathogens into our bodies

bull If these barrier layers are If these barrier layers are penetrated cells like penetrated cells like macrophages macrophages and neutrophilsand neutrophils engulf foreign engulf foreign organisms and kill them without the organisms and kill them without the need for antibodies need for antibodies

First Line of Defense-2First Line of Defense-2

bull SkinSkin provides an almost impenetrable provides an almost impenetrable biological barrier biological barrier

bull Lysozyme Lysozyme is an enzyme found in tears is an enzyme found in tears and saliva that and saliva that can break down foreign can break down foreign agents agents

bull The clotting of blood near open wounds The clotting of blood near open wounds prevents an open space for antigensprevents an open space for antigens

bull Mucus and cilia found in the nose and Mucus and cilia found in the nose and throat can catch foreign agents then throat can catch foreign agents then sweep them outside via sweep them outside via coughing coughing sneezing and vomiting sneezing and vomiting

bull The cell wall of plants consists of The cell wall of plants consists of fibrous fibrous proteinsproteins which provide a barrier to which provide a barrier to potential parasites (antigens) potential parasites (antigens)

A second line of defense-1A second line of defense-1

bull A second line of defense is the specific or A second line of defense is the specific or adaptive adaptive immune systemimmune system which may take days to respond which may take days to respond to a primary invasion to a primary invasion

bull The The production of antibodies and cell-mediated production of antibodies and cell-mediated responsesresponses may occur in which specific cells may occur in which specific cells recognize foreign pathogens and destroy themrecognize foreign pathogens and destroy them

bull The response is often more rapid because of the The response is often more rapid because of the activation of memory B and T cellsactivation of memory B and T cells

bull cells of the immune system interact with one cells of the immune system interact with one another by a variety of another by a variety of signal moleculessignal molecules

bull These signals may be proteins such as These signals may be proteins such as lymphokines cytokines and chemokineslymphokines cytokines and chemokines which which stimulate cells of the immune system stimulate cells of the immune system

Second Line of Defense-2Second Line of Defense-2

bull Second lines of defense deal with Second lines of defense deal with antigens that have bypassed the first antigens that have bypassed the first lines of defense lines of defense

bull InterferonsInterferons are a family of proteins that are a family of proteins that are released by a cell that is under are released by a cell that is under attack by an antigen attack by an antigen

bull One method of attacking antigens is by One method of attacking antigens is by phagocytosisphagocytosis where the contents of where the contents of the antigen are broken down by the antigen are broken down by molecules called phagocytesmolecules called phagocytes

Adaptive immunityAdaptive immunity

bull The The second levelsecond level of defence increases in of defence increases in strength and effectiveness with each strength and effectiveness with each encounter The foreign agent is recognised encounter The foreign agent is recognised in a specific manner and the immune system in a specific manner and the immune system acquires memory towards it acquires memory towards it

bull The first encounter with an antigen is The first encounter with an antigen is known as known as the primary responsethe primary response Re- Re-encounter with the same antigen causes a encounter with the same antigen causes a secondary responsesecondary response that is more rapid and that is more rapid and powerfulpowerful

Adaptive immunityAdaptive immunitybull As response produce antibodies to specific As response produce antibodies to specific

infectionsinfections

Some featuresSome features

ndash ndash MemoryMemorybull Each successive encounter with the same Each successive encounter with the same

pathogen improve the responsepathogen improve the response

ndash ndash Clonal selectionClonal selectionbull Select the best and matured immune cells Select the best and matured immune cells

to defend the organism against infectionsto defend the organism against infections

bull Whenever T cells and B cells are activated Whenever T cells and B cells are activated some become some become memory cellsmemory cells The next time The next time that an individual encounters that same that an individual encounters that same antigen the immune system is primed to antigen the immune system is primed to destroy it quickly This is destroy it quickly This is active immunityactive immunity

bull Long-term active immunityLong-term active immunity can be naturally can be naturally acquired by infection or artificially acquired acquired by infection or artificially acquired by vaccines by vaccines

bull Short-term passive immunityShort-term passive immunity can be can be transferred artificially from one individual to transferred artificially from one individual to another via antibody-rich serum another via antibody-rich serum

Active and Passive Acquired Active and Passive Acquired ImmunityImmunity

bull Active immunityActive immunity

ndash Conferred by recovery from infectious diseaseConferred by recovery from infectious disease

ndash Depends on persons own immune systemDepends on persons own immune system

ndash May be acquired artificially with May be acquired artificially with vaccinesvaccines

bull Passive immunityPassive immunity

ndash transferred from person to person through transfer of antibodiestransferred from person to person through transfer of antibodies

ndash Natural instances include antibodies passing across placenta from Natural instances include antibodies passing across placenta from mother to fetus (provides temporary protection) or through the mother to fetus (provides temporary protection) or through the milkmilk

ndash Transferred artificially Eg antibody injections for rabies anti Transferred artificially Eg antibody injections for rabies anti rhesus factor snake venom botulinun toxinrhesus factor snake venom botulinun toxin

bull Lymphatic vessels are responsible for flow of lymph Lymphatic vessels are responsible for flow of lymph within the lymphoid system within the lymphoid system

bull Plasma constantly leaks out of capillaries to deliver Plasma constantly leaks out of capillaries to deliver oxygen and nutrients to cells of the surrounding oxygen and nutrients to cells of the surrounding tissue Once in the tissue the plasma is now called tissue Once in the tissue the plasma is now called tissue fluidtissue fluid

bull While most of this tissue fluid re-enters capillaries While most of this tissue fluid re-enters capillaries and is returned directly to the bloodstream some and is returned directly to the bloodstream some fluid enters lymph vessels as fluid enters lymph vessels as lymph lymph

bull LYMPH-LYMPH- flows from the intercellular tissue spaces flows from the intercellular tissue spaces into lymphatic capillaries and then into a series of into lymphatic capillaries and then into a series of larger collecting vessels called larger collecting vessels called lymphatic vesselslymphatic vessels Lymphatic vessels converge into Lymphatic vessels converge into the thoracic ductthe thoracic duct which returns the fluid to the circulatory system by which returns the fluid to the circulatory system by dumping into the left dumping into the left subclavian vein subclavian vein

Thoracicduct

Overview of blood and lymph system and how Overview of blood and lymph system and how leukocytes travel from one system to anotherleukocytes travel from one system to another

Site of exchange between theblood and lymph systems

Lymph carrying antibodiesand immune cells collect in thoracic duct where the lymph empties back into the blood circulatory system

Immune cells travel back and forth from Immune cells travel back and forth from the blood and lymph circulatory systems the blood and lymph circulatory systems and interact with extra-vascular tissues and interact with extra-vascular tissues

in the process--in the process--extravasationextravasation

muscle

Lymphatic vessels Lymphatic vessels

The organs of the The organs of the immune system immune system

Kinds of lymphoid Kinds of lymphoid OrgansOrgans

Primarycentral lymphoid organsPrimarycentral lymphoid organs ndash bone marrow bone marrow ndash thymus thymus

Secondary peripheral lymphoid tissueSecondary peripheral lymphoid tissuendash lymph nodes lymph nodes ndash spleenspleenndash mucosa-associated lymphoid tissuemucosa-associated lymphoid tissue

Kinds of Lymphoid Organs Kinds of Lymphoid Organs The Lymphoid

Organs

Primary or Central organs

Secondary or Peripheral organs

1Bone marrow2Thymus gland3Bursa of fabricius

1Lymp nodes 2Spleen

3Diffuse lymphoid tissues

bull The The bone marrowbone marrow and the and the thymusthymus constitute constitute the primary lymphoid organsthe primary lymphoid organs

bull Both Both B-lymphocytesB-lymphocytes and and T-lymphocytesT-lymphocytes are are produced from stem cells in the bone produced from stem cells in the bone marrow marrow B-lymphocytes mature in the B-lymphocytes mature in the bone marrow while T-lymphocytes bone marrow while T-lymphocytes migrate to the thymus and mature migrate to the thymus and mature therethere

bull After maturation both B-lymphocytes and T-After maturation both B-lymphocytes and T-lymphocytes circulate through and lymphocytes circulate through and accumulate in accumulate in secondary lymphoid organssecondary lymphoid organs

bull The secondary lymphoid organs include lymph nodes The secondary lymphoid organs include lymph nodes and the spleen as well as lymphoid tissues and the spleen as well as lymphoid tissues

bull The lymphoid tissues include The lymphoid tissues include the tonsils the the tonsils the appendix the Peyers patchesappendix the Peyers patches in the lining of the in the lining of the small intestines (small intestines (gut-associated lymphoid tissue or gut-associated lymphoid tissue or GALTGALT) )

bull The lymphoid tissue found beneath the mucous The lymphoid tissue found beneath the mucous membranes of the bronchi (membranes of the bronchi (bronchial-associated bronchial-associated lymphoid tissue or BALTlymphoid tissue or BALT) )

bull The lymphatic tissue found in the mucous The lymphatic tissue found in the mucous membranes (membranes (mucosa-associated lymphoid tissue or mucosa-associated lymphoid tissue or MALTMALT))

bull The lymphatic tissue found beneath the skin (The lymphatic tissue found beneath the skin (skin-skin-associated lymphoid tissue or SALTassociated lymphoid tissue or SALT) )

Primary and SecondaryPrimary and Secondary Lymphoid organs Lymphoid organs

Primarycentral lymphoid Primarycentral lymphoid organs organs

BONE MARROWBONE MARROW is a central organ is a central organ where all the immune cells are where all the immune cells are born and only B cells mature born and only B cells mature (process termed as (process termed as B B lymphopoiesis) lymphopoiesis)

THYMUSTHYMUS is the other central organ is the other central organ in which T cells mature (in which T cells mature (T T lymphopoiesislymphopoiesis) )

The bone marrowThe bone marrow

Bone marrow is a spongy tissue found Bone marrow is a spongy tissue found within boneswithin bonesAll blood cells are produced within the bone All blood cells are produced within the bone marrowmarrowThe bone marrow of an adult produce about The bone marrow of an adult produce about three million red blood cells and 120000 three million red blood cells and 120000 white blood cells every second white blood cells every second All these cells originate from a small All these cells originate from a small population of stem cells which may be as population of stem cells which may be as few as one in a million of the bone marrow few as one in a million of the bone marrow cells cells

ThymuThymuss

bullThe thymus is an organ located in the The thymus is an organ located in the upper chestupper chest bullImmature lymphocytes leave the bone Immature lymphocytes leave the bone marrow and find their way to the thymus marrow and find their way to the thymus where they are ldquoeducatedrdquo to become where they are ldquoeducatedrdquo to become mature T-lymphocytesmature T-lymphocytes

ThymusThymusFlat bilobed organ situated above the heart Flat bilobed organ situated above the heart

and below the thyroid glandand below the thyroid gland Each lobe is surrounded by a capsule and is Each lobe is surrounded by a capsule and is

divided into lobules divided into lobules The lobules are separated from each other by The lobules are separated from each other by

strands of connective tissue called strands of connective tissue called trabeculaetrabeculae

Each lobule is organized into two Each lobule is organized into two compartments the compartments the cortex cortex (outer (outer compartment) the compartment) the medullamedulla (inner (inner compartment) compartment)

bull Cortex and Medulla are both crisscrossed by Cortex and Medulla are both crisscrossed by a a network of stromal cellsnetwork of stromal cells composed of composed of

bull loosely packed thymic epithelial cells loosely packed thymic epithelial cells bull interdigitating dendritic cells interdigitating dendritic cells bull macrophages macrophages

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 17: Functional organization of the Immune System

First Line of Defense-2First Line of Defense-2

bull SkinSkin provides an almost impenetrable provides an almost impenetrable biological barrier biological barrier

bull Lysozyme Lysozyme is an enzyme found in tears is an enzyme found in tears and saliva that and saliva that can break down foreign can break down foreign agents agents

bull The clotting of blood near open wounds The clotting of blood near open wounds prevents an open space for antigensprevents an open space for antigens

bull Mucus and cilia found in the nose and Mucus and cilia found in the nose and throat can catch foreign agents then throat can catch foreign agents then sweep them outside via sweep them outside via coughing coughing sneezing and vomiting sneezing and vomiting

bull The cell wall of plants consists of The cell wall of plants consists of fibrous fibrous proteinsproteins which provide a barrier to which provide a barrier to potential parasites (antigens) potential parasites (antigens)

A second line of defense-1A second line of defense-1

bull A second line of defense is the specific or A second line of defense is the specific or adaptive adaptive immune systemimmune system which may take days to respond which may take days to respond to a primary invasion to a primary invasion

bull The The production of antibodies and cell-mediated production of antibodies and cell-mediated responsesresponses may occur in which specific cells may occur in which specific cells recognize foreign pathogens and destroy themrecognize foreign pathogens and destroy them

bull The response is often more rapid because of the The response is often more rapid because of the activation of memory B and T cellsactivation of memory B and T cells

bull cells of the immune system interact with one cells of the immune system interact with one another by a variety of another by a variety of signal moleculessignal molecules

bull These signals may be proteins such as These signals may be proteins such as lymphokines cytokines and chemokineslymphokines cytokines and chemokines which which stimulate cells of the immune system stimulate cells of the immune system

Second Line of Defense-2Second Line of Defense-2

bull Second lines of defense deal with Second lines of defense deal with antigens that have bypassed the first antigens that have bypassed the first lines of defense lines of defense

bull InterferonsInterferons are a family of proteins that are a family of proteins that are released by a cell that is under are released by a cell that is under attack by an antigen attack by an antigen

bull One method of attacking antigens is by One method of attacking antigens is by phagocytosisphagocytosis where the contents of where the contents of the antigen are broken down by the antigen are broken down by molecules called phagocytesmolecules called phagocytes

Adaptive immunityAdaptive immunity

bull The The second levelsecond level of defence increases in of defence increases in strength and effectiveness with each strength and effectiveness with each encounter The foreign agent is recognised encounter The foreign agent is recognised in a specific manner and the immune system in a specific manner and the immune system acquires memory towards it acquires memory towards it

bull The first encounter with an antigen is The first encounter with an antigen is known as known as the primary responsethe primary response Re- Re-encounter with the same antigen causes a encounter with the same antigen causes a secondary responsesecondary response that is more rapid and that is more rapid and powerfulpowerful

Adaptive immunityAdaptive immunitybull As response produce antibodies to specific As response produce antibodies to specific

infectionsinfections

Some featuresSome features

ndash ndash MemoryMemorybull Each successive encounter with the same Each successive encounter with the same

pathogen improve the responsepathogen improve the response

ndash ndash Clonal selectionClonal selectionbull Select the best and matured immune cells Select the best and matured immune cells

to defend the organism against infectionsto defend the organism against infections

bull Whenever T cells and B cells are activated Whenever T cells and B cells are activated some become some become memory cellsmemory cells The next time The next time that an individual encounters that same that an individual encounters that same antigen the immune system is primed to antigen the immune system is primed to destroy it quickly This is destroy it quickly This is active immunityactive immunity

bull Long-term active immunityLong-term active immunity can be naturally can be naturally acquired by infection or artificially acquired acquired by infection or artificially acquired by vaccines by vaccines

bull Short-term passive immunityShort-term passive immunity can be can be transferred artificially from one individual to transferred artificially from one individual to another via antibody-rich serum another via antibody-rich serum

Active and Passive Acquired Active and Passive Acquired ImmunityImmunity

bull Active immunityActive immunity

ndash Conferred by recovery from infectious diseaseConferred by recovery from infectious disease

ndash Depends on persons own immune systemDepends on persons own immune system

ndash May be acquired artificially with May be acquired artificially with vaccinesvaccines

bull Passive immunityPassive immunity

ndash transferred from person to person through transfer of antibodiestransferred from person to person through transfer of antibodies

ndash Natural instances include antibodies passing across placenta from Natural instances include antibodies passing across placenta from mother to fetus (provides temporary protection) or through the mother to fetus (provides temporary protection) or through the milkmilk

ndash Transferred artificially Eg antibody injections for rabies anti Transferred artificially Eg antibody injections for rabies anti rhesus factor snake venom botulinun toxinrhesus factor snake venom botulinun toxin

bull Lymphatic vessels are responsible for flow of lymph Lymphatic vessels are responsible for flow of lymph within the lymphoid system within the lymphoid system

bull Plasma constantly leaks out of capillaries to deliver Plasma constantly leaks out of capillaries to deliver oxygen and nutrients to cells of the surrounding oxygen and nutrients to cells of the surrounding tissue Once in the tissue the plasma is now called tissue Once in the tissue the plasma is now called tissue fluidtissue fluid

bull While most of this tissue fluid re-enters capillaries While most of this tissue fluid re-enters capillaries and is returned directly to the bloodstream some and is returned directly to the bloodstream some fluid enters lymph vessels as fluid enters lymph vessels as lymph lymph

bull LYMPH-LYMPH- flows from the intercellular tissue spaces flows from the intercellular tissue spaces into lymphatic capillaries and then into a series of into lymphatic capillaries and then into a series of larger collecting vessels called larger collecting vessels called lymphatic vesselslymphatic vessels Lymphatic vessels converge into Lymphatic vessels converge into the thoracic ductthe thoracic duct which returns the fluid to the circulatory system by which returns the fluid to the circulatory system by dumping into the left dumping into the left subclavian vein subclavian vein

Thoracicduct

Overview of blood and lymph system and how Overview of blood and lymph system and how leukocytes travel from one system to anotherleukocytes travel from one system to another

Site of exchange between theblood and lymph systems

Lymph carrying antibodiesand immune cells collect in thoracic duct where the lymph empties back into the blood circulatory system

Immune cells travel back and forth from Immune cells travel back and forth from the blood and lymph circulatory systems the blood and lymph circulatory systems and interact with extra-vascular tissues and interact with extra-vascular tissues

in the process--in the process--extravasationextravasation

muscle

Lymphatic vessels Lymphatic vessels

The organs of the The organs of the immune system immune system

Kinds of lymphoid Kinds of lymphoid OrgansOrgans

Primarycentral lymphoid organsPrimarycentral lymphoid organs ndash bone marrow bone marrow ndash thymus thymus

Secondary peripheral lymphoid tissueSecondary peripheral lymphoid tissuendash lymph nodes lymph nodes ndash spleenspleenndash mucosa-associated lymphoid tissuemucosa-associated lymphoid tissue

Kinds of Lymphoid Organs Kinds of Lymphoid Organs The Lymphoid

Organs

Primary or Central organs

Secondary or Peripheral organs

1Bone marrow2Thymus gland3Bursa of fabricius

1Lymp nodes 2Spleen

3Diffuse lymphoid tissues

bull The The bone marrowbone marrow and the and the thymusthymus constitute constitute the primary lymphoid organsthe primary lymphoid organs

bull Both Both B-lymphocytesB-lymphocytes and and T-lymphocytesT-lymphocytes are are produced from stem cells in the bone produced from stem cells in the bone marrow marrow B-lymphocytes mature in the B-lymphocytes mature in the bone marrow while T-lymphocytes bone marrow while T-lymphocytes migrate to the thymus and mature migrate to the thymus and mature therethere

bull After maturation both B-lymphocytes and T-After maturation both B-lymphocytes and T-lymphocytes circulate through and lymphocytes circulate through and accumulate in accumulate in secondary lymphoid organssecondary lymphoid organs

bull The secondary lymphoid organs include lymph nodes The secondary lymphoid organs include lymph nodes and the spleen as well as lymphoid tissues and the spleen as well as lymphoid tissues

bull The lymphoid tissues include The lymphoid tissues include the tonsils the the tonsils the appendix the Peyers patchesappendix the Peyers patches in the lining of the in the lining of the small intestines (small intestines (gut-associated lymphoid tissue or gut-associated lymphoid tissue or GALTGALT) )

bull The lymphoid tissue found beneath the mucous The lymphoid tissue found beneath the mucous membranes of the bronchi (membranes of the bronchi (bronchial-associated bronchial-associated lymphoid tissue or BALTlymphoid tissue or BALT) )

bull The lymphatic tissue found in the mucous The lymphatic tissue found in the mucous membranes (membranes (mucosa-associated lymphoid tissue or mucosa-associated lymphoid tissue or MALTMALT))

bull The lymphatic tissue found beneath the skin (The lymphatic tissue found beneath the skin (skin-skin-associated lymphoid tissue or SALTassociated lymphoid tissue or SALT) )

Primary and SecondaryPrimary and Secondary Lymphoid organs Lymphoid organs

Primarycentral lymphoid Primarycentral lymphoid organs organs

BONE MARROWBONE MARROW is a central organ is a central organ where all the immune cells are where all the immune cells are born and only B cells mature born and only B cells mature (process termed as (process termed as B B lymphopoiesis) lymphopoiesis)

THYMUSTHYMUS is the other central organ is the other central organ in which T cells mature (in which T cells mature (T T lymphopoiesislymphopoiesis) )

The bone marrowThe bone marrow

Bone marrow is a spongy tissue found Bone marrow is a spongy tissue found within boneswithin bonesAll blood cells are produced within the bone All blood cells are produced within the bone marrowmarrowThe bone marrow of an adult produce about The bone marrow of an adult produce about three million red blood cells and 120000 three million red blood cells and 120000 white blood cells every second white blood cells every second All these cells originate from a small All these cells originate from a small population of stem cells which may be as population of stem cells which may be as few as one in a million of the bone marrow few as one in a million of the bone marrow cells cells

ThymuThymuss

bullThe thymus is an organ located in the The thymus is an organ located in the upper chestupper chest bullImmature lymphocytes leave the bone Immature lymphocytes leave the bone marrow and find their way to the thymus marrow and find their way to the thymus where they are ldquoeducatedrdquo to become where they are ldquoeducatedrdquo to become mature T-lymphocytesmature T-lymphocytes

ThymusThymusFlat bilobed organ situated above the heart Flat bilobed organ situated above the heart

and below the thyroid glandand below the thyroid gland Each lobe is surrounded by a capsule and is Each lobe is surrounded by a capsule and is

divided into lobules divided into lobules The lobules are separated from each other by The lobules are separated from each other by

strands of connective tissue called strands of connective tissue called trabeculaetrabeculae

Each lobule is organized into two Each lobule is organized into two compartments the compartments the cortex cortex (outer (outer compartment) the compartment) the medullamedulla (inner (inner compartment) compartment)

bull Cortex and Medulla are both crisscrossed by Cortex and Medulla are both crisscrossed by a a network of stromal cellsnetwork of stromal cells composed of composed of

bull loosely packed thymic epithelial cells loosely packed thymic epithelial cells bull interdigitating dendritic cells interdigitating dendritic cells bull macrophages macrophages

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 18: Functional organization of the Immune System

A second line of defense-1A second line of defense-1

bull A second line of defense is the specific or A second line of defense is the specific or adaptive adaptive immune systemimmune system which may take days to respond which may take days to respond to a primary invasion to a primary invasion

bull The The production of antibodies and cell-mediated production of antibodies and cell-mediated responsesresponses may occur in which specific cells may occur in which specific cells recognize foreign pathogens and destroy themrecognize foreign pathogens and destroy them

bull The response is often more rapid because of the The response is often more rapid because of the activation of memory B and T cellsactivation of memory B and T cells

bull cells of the immune system interact with one cells of the immune system interact with one another by a variety of another by a variety of signal moleculessignal molecules

bull These signals may be proteins such as These signals may be proteins such as lymphokines cytokines and chemokineslymphokines cytokines and chemokines which which stimulate cells of the immune system stimulate cells of the immune system

Second Line of Defense-2Second Line of Defense-2

bull Second lines of defense deal with Second lines of defense deal with antigens that have bypassed the first antigens that have bypassed the first lines of defense lines of defense

bull InterferonsInterferons are a family of proteins that are a family of proteins that are released by a cell that is under are released by a cell that is under attack by an antigen attack by an antigen

bull One method of attacking antigens is by One method of attacking antigens is by phagocytosisphagocytosis where the contents of where the contents of the antigen are broken down by the antigen are broken down by molecules called phagocytesmolecules called phagocytes

Adaptive immunityAdaptive immunity

bull The The second levelsecond level of defence increases in of defence increases in strength and effectiveness with each strength and effectiveness with each encounter The foreign agent is recognised encounter The foreign agent is recognised in a specific manner and the immune system in a specific manner and the immune system acquires memory towards it acquires memory towards it

bull The first encounter with an antigen is The first encounter with an antigen is known as known as the primary responsethe primary response Re- Re-encounter with the same antigen causes a encounter with the same antigen causes a secondary responsesecondary response that is more rapid and that is more rapid and powerfulpowerful

Adaptive immunityAdaptive immunitybull As response produce antibodies to specific As response produce antibodies to specific

infectionsinfections

Some featuresSome features

ndash ndash MemoryMemorybull Each successive encounter with the same Each successive encounter with the same

pathogen improve the responsepathogen improve the response

ndash ndash Clonal selectionClonal selectionbull Select the best and matured immune cells Select the best and matured immune cells

to defend the organism against infectionsto defend the organism against infections

bull Whenever T cells and B cells are activated Whenever T cells and B cells are activated some become some become memory cellsmemory cells The next time The next time that an individual encounters that same that an individual encounters that same antigen the immune system is primed to antigen the immune system is primed to destroy it quickly This is destroy it quickly This is active immunityactive immunity

bull Long-term active immunityLong-term active immunity can be naturally can be naturally acquired by infection or artificially acquired acquired by infection or artificially acquired by vaccines by vaccines

bull Short-term passive immunityShort-term passive immunity can be can be transferred artificially from one individual to transferred artificially from one individual to another via antibody-rich serum another via antibody-rich serum

Active and Passive Acquired Active and Passive Acquired ImmunityImmunity

bull Active immunityActive immunity

ndash Conferred by recovery from infectious diseaseConferred by recovery from infectious disease

ndash Depends on persons own immune systemDepends on persons own immune system

ndash May be acquired artificially with May be acquired artificially with vaccinesvaccines

bull Passive immunityPassive immunity

ndash transferred from person to person through transfer of antibodiestransferred from person to person through transfer of antibodies

ndash Natural instances include antibodies passing across placenta from Natural instances include antibodies passing across placenta from mother to fetus (provides temporary protection) or through the mother to fetus (provides temporary protection) or through the milkmilk

ndash Transferred artificially Eg antibody injections for rabies anti Transferred artificially Eg antibody injections for rabies anti rhesus factor snake venom botulinun toxinrhesus factor snake venom botulinun toxin

bull Lymphatic vessels are responsible for flow of lymph Lymphatic vessels are responsible for flow of lymph within the lymphoid system within the lymphoid system

bull Plasma constantly leaks out of capillaries to deliver Plasma constantly leaks out of capillaries to deliver oxygen and nutrients to cells of the surrounding oxygen and nutrients to cells of the surrounding tissue Once in the tissue the plasma is now called tissue Once in the tissue the plasma is now called tissue fluidtissue fluid

bull While most of this tissue fluid re-enters capillaries While most of this tissue fluid re-enters capillaries and is returned directly to the bloodstream some and is returned directly to the bloodstream some fluid enters lymph vessels as fluid enters lymph vessels as lymph lymph

bull LYMPH-LYMPH- flows from the intercellular tissue spaces flows from the intercellular tissue spaces into lymphatic capillaries and then into a series of into lymphatic capillaries and then into a series of larger collecting vessels called larger collecting vessels called lymphatic vesselslymphatic vessels Lymphatic vessels converge into Lymphatic vessels converge into the thoracic ductthe thoracic duct which returns the fluid to the circulatory system by which returns the fluid to the circulatory system by dumping into the left dumping into the left subclavian vein subclavian vein

Thoracicduct

Overview of blood and lymph system and how Overview of blood and lymph system and how leukocytes travel from one system to anotherleukocytes travel from one system to another

Site of exchange between theblood and lymph systems

Lymph carrying antibodiesand immune cells collect in thoracic duct where the lymph empties back into the blood circulatory system

Immune cells travel back and forth from Immune cells travel back and forth from the blood and lymph circulatory systems the blood and lymph circulatory systems and interact with extra-vascular tissues and interact with extra-vascular tissues

in the process--in the process--extravasationextravasation

muscle

Lymphatic vessels Lymphatic vessels

The organs of the The organs of the immune system immune system

Kinds of lymphoid Kinds of lymphoid OrgansOrgans

Primarycentral lymphoid organsPrimarycentral lymphoid organs ndash bone marrow bone marrow ndash thymus thymus

Secondary peripheral lymphoid tissueSecondary peripheral lymphoid tissuendash lymph nodes lymph nodes ndash spleenspleenndash mucosa-associated lymphoid tissuemucosa-associated lymphoid tissue

Kinds of Lymphoid Organs Kinds of Lymphoid Organs The Lymphoid

Organs

Primary or Central organs

Secondary or Peripheral organs

1Bone marrow2Thymus gland3Bursa of fabricius

1Lymp nodes 2Spleen

3Diffuse lymphoid tissues

bull The The bone marrowbone marrow and the and the thymusthymus constitute constitute the primary lymphoid organsthe primary lymphoid organs

bull Both Both B-lymphocytesB-lymphocytes and and T-lymphocytesT-lymphocytes are are produced from stem cells in the bone produced from stem cells in the bone marrow marrow B-lymphocytes mature in the B-lymphocytes mature in the bone marrow while T-lymphocytes bone marrow while T-lymphocytes migrate to the thymus and mature migrate to the thymus and mature therethere

bull After maturation both B-lymphocytes and T-After maturation both B-lymphocytes and T-lymphocytes circulate through and lymphocytes circulate through and accumulate in accumulate in secondary lymphoid organssecondary lymphoid organs

bull The secondary lymphoid organs include lymph nodes The secondary lymphoid organs include lymph nodes and the spleen as well as lymphoid tissues and the spleen as well as lymphoid tissues

bull The lymphoid tissues include The lymphoid tissues include the tonsils the the tonsils the appendix the Peyers patchesappendix the Peyers patches in the lining of the in the lining of the small intestines (small intestines (gut-associated lymphoid tissue or gut-associated lymphoid tissue or GALTGALT) )

bull The lymphoid tissue found beneath the mucous The lymphoid tissue found beneath the mucous membranes of the bronchi (membranes of the bronchi (bronchial-associated bronchial-associated lymphoid tissue or BALTlymphoid tissue or BALT) )

bull The lymphatic tissue found in the mucous The lymphatic tissue found in the mucous membranes (membranes (mucosa-associated lymphoid tissue or mucosa-associated lymphoid tissue or MALTMALT))

bull The lymphatic tissue found beneath the skin (The lymphatic tissue found beneath the skin (skin-skin-associated lymphoid tissue or SALTassociated lymphoid tissue or SALT) )

Primary and SecondaryPrimary and Secondary Lymphoid organs Lymphoid organs

Primarycentral lymphoid Primarycentral lymphoid organs organs

BONE MARROWBONE MARROW is a central organ is a central organ where all the immune cells are where all the immune cells are born and only B cells mature born and only B cells mature (process termed as (process termed as B B lymphopoiesis) lymphopoiesis)

THYMUSTHYMUS is the other central organ is the other central organ in which T cells mature (in which T cells mature (T T lymphopoiesislymphopoiesis) )

The bone marrowThe bone marrow

Bone marrow is a spongy tissue found Bone marrow is a spongy tissue found within boneswithin bonesAll blood cells are produced within the bone All blood cells are produced within the bone marrowmarrowThe bone marrow of an adult produce about The bone marrow of an adult produce about three million red blood cells and 120000 three million red blood cells and 120000 white blood cells every second white blood cells every second All these cells originate from a small All these cells originate from a small population of stem cells which may be as population of stem cells which may be as few as one in a million of the bone marrow few as one in a million of the bone marrow cells cells

ThymuThymuss

bullThe thymus is an organ located in the The thymus is an organ located in the upper chestupper chest bullImmature lymphocytes leave the bone Immature lymphocytes leave the bone marrow and find their way to the thymus marrow and find their way to the thymus where they are ldquoeducatedrdquo to become where they are ldquoeducatedrdquo to become mature T-lymphocytesmature T-lymphocytes

ThymusThymusFlat bilobed organ situated above the heart Flat bilobed organ situated above the heart

and below the thyroid glandand below the thyroid gland Each lobe is surrounded by a capsule and is Each lobe is surrounded by a capsule and is

divided into lobules divided into lobules The lobules are separated from each other by The lobules are separated from each other by

strands of connective tissue called strands of connective tissue called trabeculaetrabeculae

Each lobule is organized into two Each lobule is organized into two compartments the compartments the cortex cortex (outer (outer compartment) the compartment) the medullamedulla (inner (inner compartment) compartment)

bull Cortex and Medulla are both crisscrossed by Cortex and Medulla are both crisscrossed by a a network of stromal cellsnetwork of stromal cells composed of composed of

bull loosely packed thymic epithelial cells loosely packed thymic epithelial cells bull interdigitating dendritic cells interdigitating dendritic cells bull macrophages macrophages

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 19: Functional organization of the Immune System

Second Line of Defense-2Second Line of Defense-2

bull Second lines of defense deal with Second lines of defense deal with antigens that have bypassed the first antigens that have bypassed the first lines of defense lines of defense

bull InterferonsInterferons are a family of proteins that are a family of proteins that are released by a cell that is under are released by a cell that is under attack by an antigen attack by an antigen

bull One method of attacking antigens is by One method of attacking antigens is by phagocytosisphagocytosis where the contents of where the contents of the antigen are broken down by the antigen are broken down by molecules called phagocytesmolecules called phagocytes

Adaptive immunityAdaptive immunity

bull The The second levelsecond level of defence increases in of defence increases in strength and effectiveness with each strength and effectiveness with each encounter The foreign agent is recognised encounter The foreign agent is recognised in a specific manner and the immune system in a specific manner and the immune system acquires memory towards it acquires memory towards it

bull The first encounter with an antigen is The first encounter with an antigen is known as known as the primary responsethe primary response Re- Re-encounter with the same antigen causes a encounter with the same antigen causes a secondary responsesecondary response that is more rapid and that is more rapid and powerfulpowerful

Adaptive immunityAdaptive immunitybull As response produce antibodies to specific As response produce antibodies to specific

infectionsinfections

Some featuresSome features

ndash ndash MemoryMemorybull Each successive encounter with the same Each successive encounter with the same

pathogen improve the responsepathogen improve the response

ndash ndash Clonal selectionClonal selectionbull Select the best and matured immune cells Select the best and matured immune cells

to defend the organism against infectionsto defend the organism against infections

bull Whenever T cells and B cells are activated Whenever T cells and B cells are activated some become some become memory cellsmemory cells The next time The next time that an individual encounters that same that an individual encounters that same antigen the immune system is primed to antigen the immune system is primed to destroy it quickly This is destroy it quickly This is active immunityactive immunity

bull Long-term active immunityLong-term active immunity can be naturally can be naturally acquired by infection or artificially acquired acquired by infection or artificially acquired by vaccines by vaccines

bull Short-term passive immunityShort-term passive immunity can be can be transferred artificially from one individual to transferred artificially from one individual to another via antibody-rich serum another via antibody-rich serum

Active and Passive Acquired Active and Passive Acquired ImmunityImmunity

bull Active immunityActive immunity

ndash Conferred by recovery from infectious diseaseConferred by recovery from infectious disease

ndash Depends on persons own immune systemDepends on persons own immune system

ndash May be acquired artificially with May be acquired artificially with vaccinesvaccines

bull Passive immunityPassive immunity

ndash transferred from person to person through transfer of antibodiestransferred from person to person through transfer of antibodies

ndash Natural instances include antibodies passing across placenta from Natural instances include antibodies passing across placenta from mother to fetus (provides temporary protection) or through the mother to fetus (provides temporary protection) or through the milkmilk

ndash Transferred artificially Eg antibody injections for rabies anti Transferred artificially Eg antibody injections for rabies anti rhesus factor snake venom botulinun toxinrhesus factor snake venom botulinun toxin

bull Lymphatic vessels are responsible for flow of lymph Lymphatic vessels are responsible for flow of lymph within the lymphoid system within the lymphoid system

bull Plasma constantly leaks out of capillaries to deliver Plasma constantly leaks out of capillaries to deliver oxygen and nutrients to cells of the surrounding oxygen and nutrients to cells of the surrounding tissue Once in the tissue the plasma is now called tissue Once in the tissue the plasma is now called tissue fluidtissue fluid

bull While most of this tissue fluid re-enters capillaries While most of this tissue fluid re-enters capillaries and is returned directly to the bloodstream some and is returned directly to the bloodstream some fluid enters lymph vessels as fluid enters lymph vessels as lymph lymph

bull LYMPH-LYMPH- flows from the intercellular tissue spaces flows from the intercellular tissue spaces into lymphatic capillaries and then into a series of into lymphatic capillaries and then into a series of larger collecting vessels called larger collecting vessels called lymphatic vesselslymphatic vessels Lymphatic vessels converge into Lymphatic vessels converge into the thoracic ductthe thoracic duct which returns the fluid to the circulatory system by which returns the fluid to the circulatory system by dumping into the left dumping into the left subclavian vein subclavian vein

Thoracicduct

Overview of blood and lymph system and how Overview of blood and lymph system and how leukocytes travel from one system to anotherleukocytes travel from one system to another

Site of exchange between theblood and lymph systems

Lymph carrying antibodiesand immune cells collect in thoracic duct where the lymph empties back into the blood circulatory system

Immune cells travel back and forth from Immune cells travel back and forth from the blood and lymph circulatory systems the blood and lymph circulatory systems and interact with extra-vascular tissues and interact with extra-vascular tissues

in the process--in the process--extravasationextravasation

muscle

Lymphatic vessels Lymphatic vessels

The organs of the The organs of the immune system immune system

Kinds of lymphoid Kinds of lymphoid OrgansOrgans

Primarycentral lymphoid organsPrimarycentral lymphoid organs ndash bone marrow bone marrow ndash thymus thymus

Secondary peripheral lymphoid tissueSecondary peripheral lymphoid tissuendash lymph nodes lymph nodes ndash spleenspleenndash mucosa-associated lymphoid tissuemucosa-associated lymphoid tissue

Kinds of Lymphoid Organs Kinds of Lymphoid Organs The Lymphoid

Organs

Primary or Central organs

Secondary or Peripheral organs

1Bone marrow2Thymus gland3Bursa of fabricius

1Lymp nodes 2Spleen

3Diffuse lymphoid tissues

bull The The bone marrowbone marrow and the and the thymusthymus constitute constitute the primary lymphoid organsthe primary lymphoid organs

bull Both Both B-lymphocytesB-lymphocytes and and T-lymphocytesT-lymphocytes are are produced from stem cells in the bone produced from stem cells in the bone marrow marrow B-lymphocytes mature in the B-lymphocytes mature in the bone marrow while T-lymphocytes bone marrow while T-lymphocytes migrate to the thymus and mature migrate to the thymus and mature therethere

bull After maturation both B-lymphocytes and T-After maturation both B-lymphocytes and T-lymphocytes circulate through and lymphocytes circulate through and accumulate in accumulate in secondary lymphoid organssecondary lymphoid organs

bull The secondary lymphoid organs include lymph nodes The secondary lymphoid organs include lymph nodes and the spleen as well as lymphoid tissues and the spleen as well as lymphoid tissues

bull The lymphoid tissues include The lymphoid tissues include the tonsils the the tonsils the appendix the Peyers patchesappendix the Peyers patches in the lining of the in the lining of the small intestines (small intestines (gut-associated lymphoid tissue or gut-associated lymphoid tissue or GALTGALT) )

bull The lymphoid tissue found beneath the mucous The lymphoid tissue found beneath the mucous membranes of the bronchi (membranes of the bronchi (bronchial-associated bronchial-associated lymphoid tissue or BALTlymphoid tissue or BALT) )

bull The lymphatic tissue found in the mucous The lymphatic tissue found in the mucous membranes (membranes (mucosa-associated lymphoid tissue or mucosa-associated lymphoid tissue or MALTMALT))

bull The lymphatic tissue found beneath the skin (The lymphatic tissue found beneath the skin (skin-skin-associated lymphoid tissue or SALTassociated lymphoid tissue or SALT) )

Primary and SecondaryPrimary and Secondary Lymphoid organs Lymphoid organs

Primarycentral lymphoid Primarycentral lymphoid organs organs

BONE MARROWBONE MARROW is a central organ is a central organ where all the immune cells are where all the immune cells are born and only B cells mature born and only B cells mature (process termed as (process termed as B B lymphopoiesis) lymphopoiesis)

THYMUSTHYMUS is the other central organ is the other central organ in which T cells mature (in which T cells mature (T T lymphopoiesislymphopoiesis) )

The bone marrowThe bone marrow

Bone marrow is a spongy tissue found Bone marrow is a spongy tissue found within boneswithin bonesAll blood cells are produced within the bone All blood cells are produced within the bone marrowmarrowThe bone marrow of an adult produce about The bone marrow of an adult produce about three million red blood cells and 120000 three million red blood cells and 120000 white blood cells every second white blood cells every second All these cells originate from a small All these cells originate from a small population of stem cells which may be as population of stem cells which may be as few as one in a million of the bone marrow few as one in a million of the bone marrow cells cells

ThymuThymuss

bullThe thymus is an organ located in the The thymus is an organ located in the upper chestupper chest bullImmature lymphocytes leave the bone Immature lymphocytes leave the bone marrow and find their way to the thymus marrow and find their way to the thymus where they are ldquoeducatedrdquo to become where they are ldquoeducatedrdquo to become mature T-lymphocytesmature T-lymphocytes

ThymusThymusFlat bilobed organ situated above the heart Flat bilobed organ situated above the heart

and below the thyroid glandand below the thyroid gland Each lobe is surrounded by a capsule and is Each lobe is surrounded by a capsule and is

divided into lobules divided into lobules The lobules are separated from each other by The lobules are separated from each other by

strands of connective tissue called strands of connective tissue called trabeculaetrabeculae

Each lobule is organized into two Each lobule is organized into two compartments the compartments the cortex cortex (outer (outer compartment) the compartment) the medullamedulla (inner (inner compartment) compartment)

bull Cortex and Medulla are both crisscrossed by Cortex and Medulla are both crisscrossed by a a network of stromal cellsnetwork of stromal cells composed of composed of

bull loosely packed thymic epithelial cells loosely packed thymic epithelial cells bull interdigitating dendritic cells interdigitating dendritic cells bull macrophages macrophages

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 20: Functional organization of the Immune System

Adaptive immunityAdaptive immunity

bull The The second levelsecond level of defence increases in of defence increases in strength and effectiveness with each strength and effectiveness with each encounter The foreign agent is recognised encounter The foreign agent is recognised in a specific manner and the immune system in a specific manner and the immune system acquires memory towards it acquires memory towards it

bull The first encounter with an antigen is The first encounter with an antigen is known as known as the primary responsethe primary response Re- Re-encounter with the same antigen causes a encounter with the same antigen causes a secondary responsesecondary response that is more rapid and that is more rapid and powerfulpowerful

Adaptive immunityAdaptive immunitybull As response produce antibodies to specific As response produce antibodies to specific

infectionsinfections

Some featuresSome features

ndash ndash MemoryMemorybull Each successive encounter with the same Each successive encounter with the same

pathogen improve the responsepathogen improve the response

ndash ndash Clonal selectionClonal selectionbull Select the best and matured immune cells Select the best and matured immune cells

to defend the organism against infectionsto defend the organism against infections

bull Whenever T cells and B cells are activated Whenever T cells and B cells are activated some become some become memory cellsmemory cells The next time The next time that an individual encounters that same that an individual encounters that same antigen the immune system is primed to antigen the immune system is primed to destroy it quickly This is destroy it quickly This is active immunityactive immunity

bull Long-term active immunityLong-term active immunity can be naturally can be naturally acquired by infection or artificially acquired acquired by infection or artificially acquired by vaccines by vaccines

bull Short-term passive immunityShort-term passive immunity can be can be transferred artificially from one individual to transferred artificially from one individual to another via antibody-rich serum another via antibody-rich serum

Active and Passive Acquired Active and Passive Acquired ImmunityImmunity

bull Active immunityActive immunity

ndash Conferred by recovery from infectious diseaseConferred by recovery from infectious disease

ndash Depends on persons own immune systemDepends on persons own immune system

ndash May be acquired artificially with May be acquired artificially with vaccinesvaccines

bull Passive immunityPassive immunity

ndash transferred from person to person through transfer of antibodiestransferred from person to person through transfer of antibodies

ndash Natural instances include antibodies passing across placenta from Natural instances include antibodies passing across placenta from mother to fetus (provides temporary protection) or through the mother to fetus (provides temporary protection) or through the milkmilk

ndash Transferred artificially Eg antibody injections for rabies anti Transferred artificially Eg antibody injections for rabies anti rhesus factor snake venom botulinun toxinrhesus factor snake venom botulinun toxin

bull Lymphatic vessels are responsible for flow of lymph Lymphatic vessels are responsible for flow of lymph within the lymphoid system within the lymphoid system

bull Plasma constantly leaks out of capillaries to deliver Plasma constantly leaks out of capillaries to deliver oxygen and nutrients to cells of the surrounding oxygen and nutrients to cells of the surrounding tissue Once in the tissue the plasma is now called tissue Once in the tissue the plasma is now called tissue fluidtissue fluid

bull While most of this tissue fluid re-enters capillaries While most of this tissue fluid re-enters capillaries and is returned directly to the bloodstream some and is returned directly to the bloodstream some fluid enters lymph vessels as fluid enters lymph vessels as lymph lymph

bull LYMPH-LYMPH- flows from the intercellular tissue spaces flows from the intercellular tissue spaces into lymphatic capillaries and then into a series of into lymphatic capillaries and then into a series of larger collecting vessels called larger collecting vessels called lymphatic vesselslymphatic vessels Lymphatic vessels converge into Lymphatic vessels converge into the thoracic ductthe thoracic duct which returns the fluid to the circulatory system by which returns the fluid to the circulatory system by dumping into the left dumping into the left subclavian vein subclavian vein

Thoracicduct

Overview of blood and lymph system and how Overview of blood and lymph system and how leukocytes travel from one system to anotherleukocytes travel from one system to another

Site of exchange between theblood and lymph systems

Lymph carrying antibodiesand immune cells collect in thoracic duct where the lymph empties back into the blood circulatory system

Immune cells travel back and forth from Immune cells travel back and forth from the blood and lymph circulatory systems the blood and lymph circulatory systems and interact with extra-vascular tissues and interact with extra-vascular tissues

in the process--in the process--extravasationextravasation

muscle

Lymphatic vessels Lymphatic vessels

The organs of the The organs of the immune system immune system

Kinds of lymphoid Kinds of lymphoid OrgansOrgans

Primarycentral lymphoid organsPrimarycentral lymphoid organs ndash bone marrow bone marrow ndash thymus thymus

Secondary peripheral lymphoid tissueSecondary peripheral lymphoid tissuendash lymph nodes lymph nodes ndash spleenspleenndash mucosa-associated lymphoid tissuemucosa-associated lymphoid tissue

Kinds of Lymphoid Organs Kinds of Lymphoid Organs The Lymphoid

Organs

Primary or Central organs

Secondary or Peripheral organs

1Bone marrow2Thymus gland3Bursa of fabricius

1Lymp nodes 2Spleen

3Diffuse lymphoid tissues

bull The The bone marrowbone marrow and the and the thymusthymus constitute constitute the primary lymphoid organsthe primary lymphoid organs

bull Both Both B-lymphocytesB-lymphocytes and and T-lymphocytesT-lymphocytes are are produced from stem cells in the bone produced from stem cells in the bone marrow marrow B-lymphocytes mature in the B-lymphocytes mature in the bone marrow while T-lymphocytes bone marrow while T-lymphocytes migrate to the thymus and mature migrate to the thymus and mature therethere

bull After maturation both B-lymphocytes and T-After maturation both B-lymphocytes and T-lymphocytes circulate through and lymphocytes circulate through and accumulate in accumulate in secondary lymphoid organssecondary lymphoid organs

bull The secondary lymphoid organs include lymph nodes The secondary lymphoid organs include lymph nodes and the spleen as well as lymphoid tissues and the spleen as well as lymphoid tissues

bull The lymphoid tissues include The lymphoid tissues include the tonsils the the tonsils the appendix the Peyers patchesappendix the Peyers patches in the lining of the in the lining of the small intestines (small intestines (gut-associated lymphoid tissue or gut-associated lymphoid tissue or GALTGALT) )

bull The lymphoid tissue found beneath the mucous The lymphoid tissue found beneath the mucous membranes of the bronchi (membranes of the bronchi (bronchial-associated bronchial-associated lymphoid tissue or BALTlymphoid tissue or BALT) )

bull The lymphatic tissue found in the mucous The lymphatic tissue found in the mucous membranes (membranes (mucosa-associated lymphoid tissue or mucosa-associated lymphoid tissue or MALTMALT))

bull The lymphatic tissue found beneath the skin (The lymphatic tissue found beneath the skin (skin-skin-associated lymphoid tissue or SALTassociated lymphoid tissue or SALT) )

Primary and SecondaryPrimary and Secondary Lymphoid organs Lymphoid organs

Primarycentral lymphoid Primarycentral lymphoid organs organs

BONE MARROWBONE MARROW is a central organ is a central organ where all the immune cells are where all the immune cells are born and only B cells mature born and only B cells mature (process termed as (process termed as B B lymphopoiesis) lymphopoiesis)

THYMUSTHYMUS is the other central organ is the other central organ in which T cells mature (in which T cells mature (T T lymphopoiesislymphopoiesis) )

The bone marrowThe bone marrow

Bone marrow is a spongy tissue found Bone marrow is a spongy tissue found within boneswithin bonesAll blood cells are produced within the bone All blood cells are produced within the bone marrowmarrowThe bone marrow of an adult produce about The bone marrow of an adult produce about three million red blood cells and 120000 three million red blood cells and 120000 white blood cells every second white blood cells every second All these cells originate from a small All these cells originate from a small population of stem cells which may be as population of stem cells which may be as few as one in a million of the bone marrow few as one in a million of the bone marrow cells cells

ThymuThymuss

bullThe thymus is an organ located in the The thymus is an organ located in the upper chestupper chest bullImmature lymphocytes leave the bone Immature lymphocytes leave the bone marrow and find their way to the thymus marrow and find their way to the thymus where they are ldquoeducatedrdquo to become where they are ldquoeducatedrdquo to become mature T-lymphocytesmature T-lymphocytes

ThymusThymusFlat bilobed organ situated above the heart Flat bilobed organ situated above the heart

and below the thyroid glandand below the thyroid gland Each lobe is surrounded by a capsule and is Each lobe is surrounded by a capsule and is

divided into lobules divided into lobules The lobules are separated from each other by The lobules are separated from each other by

strands of connective tissue called strands of connective tissue called trabeculaetrabeculae

Each lobule is organized into two Each lobule is organized into two compartments the compartments the cortex cortex (outer (outer compartment) the compartment) the medullamedulla (inner (inner compartment) compartment)

bull Cortex and Medulla are both crisscrossed by Cortex and Medulla are both crisscrossed by a a network of stromal cellsnetwork of stromal cells composed of composed of

bull loosely packed thymic epithelial cells loosely packed thymic epithelial cells bull interdigitating dendritic cells interdigitating dendritic cells bull macrophages macrophages

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 21: Functional organization of the Immune System

Adaptive immunityAdaptive immunitybull As response produce antibodies to specific As response produce antibodies to specific

infectionsinfections

Some featuresSome features

ndash ndash MemoryMemorybull Each successive encounter with the same Each successive encounter with the same

pathogen improve the responsepathogen improve the response

ndash ndash Clonal selectionClonal selectionbull Select the best and matured immune cells Select the best and matured immune cells

to defend the organism against infectionsto defend the organism against infections

bull Whenever T cells and B cells are activated Whenever T cells and B cells are activated some become some become memory cellsmemory cells The next time The next time that an individual encounters that same that an individual encounters that same antigen the immune system is primed to antigen the immune system is primed to destroy it quickly This is destroy it quickly This is active immunityactive immunity

bull Long-term active immunityLong-term active immunity can be naturally can be naturally acquired by infection or artificially acquired acquired by infection or artificially acquired by vaccines by vaccines

bull Short-term passive immunityShort-term passive immunity can be can be transferred artificially from one individual to transferred artificially from one individual to another via antibody-rich serum another via antibody-rich serum

Active and Passive Acquired Active and Passive Acquired ImmunityImmunity

bull Active immunityActive immunity

ndash Conferred by recovery from infectious diseaseConferred by recovery from infectious disease

ndash Depends on persons own immune systemDepends on persons own immune system

ndash May be acquired artificially with May be acquired artificially with vaccinesvaccines

bull Passive immunityPassive immunity

ndash transferred from person to person through transfer of antibodiestransferred from person to person through transfer of antibodies

ndash Natural instances include antibodies passing across placenta from Natural instances include antibodies passing across placenta from mother to fetus (provides temporary protection) or through the mother to fetus (provides temporary protection) or through the milkmilk

ndash Transferred artificially Eg antibody injections for rabies anti Transferred artificially Eg antibody injections for rabies anti rhesus factor snake venom botulinun toxinrhesus factor snake venom botulinun toxin

bull Lymphatic vessels are responsible for flow of lymph Lymphatic vessels are responsible for flow of lymph within the lymphoid system within the lymphoid system

bull Plasma constantly leaks out of capillaries to deliver Plasma constantly leaks out of capillaries to deliver oxygen and nutrients to cells of the surrounding oxygen and nutrients to cells of the surrounding tissue Once in the tissue the plasma is now called tissue Once in the tissue the plasma is now called tissue fluidtissue fluid

bull While most of this tissue fluid re-enters capillaries While most of this tissue fluid re-enters capillaries and is returned directly to the bloodstream some and is returned directly to the bloodstream some fluid enters lymph vessels as fluid enters lymph vessels as lymph lymph

bull LYMPH-LYMPH- flows from the intercellular tissue spaces flows from the intercellular tissue spaces into lymphatic capillaries and then into a series of into lymphatic capillaries and then into a series of larger collecting vessels called larger collecting vessels called lymphatic vesselslymphatic vessels Lymphatic vessels converge into Lymphatic vessels converge into the thoracic ductthe thoracic duct which returns the fluid to the circulatory system by which returns the fluid to the circulatory system by dumping into the left dumping into the left subclavian vein subclavian vein

Thoracicduct

Overview of blood and lymph system and how Overview of blood and lymph system and how leukocytes travel from one system to anotherleukocytes travel from one system to another

Site of exchange between theblood and lymph systems

Lymph carrying antibodiesand immune cells collect in thoracic duct where the lymph empties back into the blood circulatory system

Immune cells travel back and forth from Immune cells travel back and forth from the blood and lymph circulatory systems the blood and lymph circulatory systems and interact with extra-vascular tissues and interact with extra-vascular tissues

in the process--in the process--extravasationextravasation

muscle

Lymphatic vessels Lymphatic vessels

The organs of the The organs of the immune system immune system

Kinds of lymphoid Kinds of lymphoid OrgansOrgans

Primarycentral lymphoid organsPrimarycentral lymphoid organs ndash bone marrow bone marrow ndash thymus thymus

Secondary peripheral lymphoid tissueSecondary peripheral lymphoid tissuendash lymph nodes lymph nodes ndash spleenspleenndash mucosa-associated lymphoid tissuemucosa-associated lymphoid tissue

Kinds of Lymphoid Organs Kinds of Lymphoid Organs The Lymphoid

Organs

Primary or Central organs

Secondary or Peripheral organs

1Bone marrow2Thymus gland3Bursa of fabricius

1Lymp nodes 2Spleen

3Diffuse lymphoid tissues

bull The The bone marrowbone marrow and the and the thymusthymus constitute constitute the primary lymphoid organsthe primary lymphoid organs

bull Both Both B-lymphocytesB-lymphocytes and and T-lymphocytesT-lymphocytes are are produced from stem cells in the bone produced from stem cells in the bone marrow marrow B-lymphocytes mature in the B-lymphocytes mature in the bone marrow while T-lymphocytes bone marrow while T-lymphocytes migrate to the thymus and mature migrate to the thymus and mature therethere

bull After maturation both B-lymphocytes and T-After maturation both B-lymphocytes and T-lymphocytes circulate through and lymphocytes circulate through and accumulate in accumulate in secondary lymphoid organssecondary lymphoid organs

bull The secondary lymphoid organs include lymph nodes The secondary lymphoid organs include lymph nodes and the spleen as well as lymphoid tissues and the spleen as well as lymphoid tissues

bull The lymphoid tissues include The lymphoid tissues include the tonsils the the tonsils the appendix the Peyers patchesappendix the Peyers patches in the lining of the in the lining of the small intestines (small intestines (gut-associated lymphoid tissue or gut-associated lymphoid tissue or GALTGALT) )

bull The lymphoid tissue found beneath the mucous The lymphoid tissue found beneath the mucous membranes of the bronchi (membranes of the bronchi (bronchial-associated bronchial-associated lymphoid tissue or BALTlymphoid tissue or BALT) )

bull The lymphatic tissue found in the mucous The lymphatic tissue found in the mucous membranes (membranes (mucosa-associated lymphoid tissue or mucosa-associated lymphoid tissue or MALTMALT))

bull The lymphatic tissue found beneath the skin (The lymphatic tissue found beneath the skin (skin-skin-associated lymphoid tissue or SALTassociated lymphoid tissue or SALT) )

Primary and SecondaryPrimary and Secondary Lymphoid organs Lymphoid organs

Primarycentral lymphoid Primarycentral lymphoid organs organs

BONE MARROWBONE MARROW is a central organ is a central organ where all the immune cells are where all the immune cells are born and only B cells mature born and only B cells mature (process termed as (process termed as B B lymphopoiesis) lymphopoiesis)

THYMUSTHYMUS is the other central organ is the other central organ in which T cells mature (in which T cells mature (T T lymphopoiesislymphopoiesis) )

The bone marrowThe bone marrow

Bone marrow is a spongy tissue found Bone marrow is a spongy tissue found within boneswithin bonesAll blood cells are produced within the bone All blood cells are produced within the bone marrowmarrowThe bone marrow of an adult produce about The bone marrow of an adult produce about three million red blood cells and 120000 three million red blood cells and 120000 white blood cells every second white blood cells every second All these cells originate from a small All these cells originate from a small population of stem cells which may be as population of stem cells which may be as few as one in a million of the bone marrow few as one in a million of the bone marrow cells cells

ThymuThymuss

bullThe thymus is an organ located in the The thymus is an organ located in the upper chestupper chest bullImmature lymphocytes leave the bone Immature lymphocytes leave the bone marrow and find their way to the thymus marrow and find their way to the thymus where they are ldquoeducatedrdquo to become where they are ldquoeducatedrdquo to become mature T-lymphocytesmature T-lymphocytes

ThymusThymusFlat bilobed organ situated above the heart Flat bilobed organ situated above the heart

and below the thyroid glandand below the thyroid gland Each lobe is surrounded by a capsule and is Each lobe is surrounded by a capsule and is

divided into lobules divided into lobules The lobules are separated from each other by The lobules are separated from each other by

strands of connective tissue called strands of connective tissue called trabeculaetrabeculae

Each lobule is organized into two Each lobule is organized into two compartments the compartments the cortex cortex (outer (outer compartment) the compartment) the medullamedulla (inner (inner compartment) compartment)

bull Cortex and Medulla are both crisscrossed by Cortex and Medulla are both crisscrossed by a a network of stromal cellsnetwork of stromal cells composed of composed of

bull loosely packed thymic epithelial cells loosely packed thymic epithelial cells bull interdigitating dendritic cells interdigitating dendritic cells bull macrophages macrophages

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 22: Functional organization of the Immune System

bull Whenever T cells and B cells are activated Whenever T cells and B cells are activated some become some become memory cellsmemory cells The next time The next time that an individual encounters that same that an individual encounters that same antigen the immune system is primed to antigen the immune system is primed to destroy it quickly This is destroy it quickly This is active immunityactive immunity

bull Long-term active immunityLong-term active immunity can be naturally can be naturally acquired by infection or artificially acquired acquired by infection or artificially acquired by vaccines by vaccines

bull Short-term passive immunityShort-term passive immunity can be can be transferred artificially from one individual to transferred artificially from one individual to another via antibody-rich serum another via antibody-rich serum

Active and Passive Acquired Active and Passive Acquired ImmunityImmunity

bull Active immunityActive immunity

ndash Conferred by recovery from infectious diseaseConferred by recovery from infectious disease

ndash Depends on persons own immune systemDepends on persons own immune system

ndash May be acquired artificially with May be acquired artificially with vaccinesvaccines

bull Passive immunityPassive immunity

ndash transferred from person to person through transfer of antibodiestransferred from person to person through transfer of antibodies

ndash Natural instances include antibodies passing across placenta from Natural instances include antibodies passing across placenta from mother to fetus (provides temporary protection) or through the mother to fetus (provides temporary protection) or through the milkmilk

ndash Transferred artificially Eg antibody injections for rabies anti Transferred artificially Eg antibody injections for rabies anti rhesus factor snake venom botulinun toxinrhesus factor snake venom botulinun toxin

bull Lymphatic vessels are responsible for flow of lymph Lymphatic vessels are responsible for flow of lymph within the lymphoid system within the lymphoid system

bull Plasma constantly leaks out of capillaries to deliver Plasma constantly leaks out of capillaries to deliver oxygen and nutrients to cells of the surrounding oxygen and nutrients to cells of the surrounding tissue Once in the tissue the plasma is now called tissue Once in the tissue the plasma is now called tissue fluidtissue fluid

bull While most of this tissue fluid re-enters capillaries While most of this tissue fluid re-enters capillaries and is returned directly to the bloodstream some and is returned directly to the bloodstream some fluid enters lymph vessels as fluid enters lymph vessels as lymph lymph

bull LYMPH-LYMPH- flows from the intercellular tissue spaces flows from the intercellular tissue spaces into lymphatic capillaries and then into a series of into lymphatic capillaries and then into a series of larger collecting vessels called larger collecting vessels called lymphatic vesselslymphatic vessels Lymphatic vessels converge into Lymphatic vessels converge into the thoracic ductthe thoracic duct which returns the fluid to the circulatory system by which returns the fluid to the circulatory system by dumping into the left dumping into the left subclavian vein subclavian vein

Thoracicduct

Overview of blood and lymph system and how Overview of blood and lymph system and how leukocytes travel from one system to anotherleukocytes travel from one system to another

Site of exchange between theblood and lymph systems

Lymph carrying antibodiesand immune cells collect in thoracic duct where the lymph empties back into the blood circulatory system

Immune cells travel back and forth from Immune cells travel back and forth from the blood and lymph circulatory systems the blood and lymph circulatory systems and interact with extra-vascular tissues and interact with extra-vascular tissues

in the process--in the process--extravasationextravasation

muscle

Lymphatic vessels Lymphatic vessels

The organs of the The organs of the immune system immune system

Kinds of lymphoid Kinds of lymphoid OrgansOrgans

Primarycentral lymphoid organsPrimarycentral lymphoid organs ndash bone marrow bone marrow ndash thymus thymus

Secondary peripheral lymphoid tissueSecondary peripheral lymphoid tissuendash lymph nodes lymph nodes ndash spleenspleenndash mucosa-associated lymphoid tissuemucosa-associated lymphoid tissue

Kinds of Lymphoid Organs Kinds of Lymphoid Organs The Lymphoid

Organs

Primary or Central organs

Secondary or Peripheral organs

1Bone marrow2Thymus gland3Bursa of fabricius

1Lymp nodes 2Spleen

3Diffuse lymphoid tissues

bull The The bone marrowbone marrow and the and the thymusthymus constitute constitute the primary lymphoid organsthe primary lymphoid organs

bull Both Both B-lymphocytesB-lymphocytes and and T-lymphocytesT-lymphocytes are are produced from stem cells in the bone produced from stem cells in the bone marrow marrow B-lymphocytes mature in the B-lymphocytes mature in the bone marrow while T-lymphocytes bone marrow while T-lymphocytes migrate to the thymus and mature migrate to the thymus and mature therethere

bull After maturation both B-lymphocytes and T-After maturation both B-lymphocytes and T-lymphocytes circulate through and lymphocytes circulate through and accumulate in accumulate in secondary lymphoid organssecondary lymphoid organs

bull The secondary lymphoid organs include lymph nodes The secondary lymphoid organs include lymph nodes and the spleen as well as lymphoid tissues and the spleen as well as lymphoid tissues

bull The lymphoid tissues include The lymphoid tissues include the tonsils the the tonsils the appendix the Peyers patchesappendix the Peyers patches in the lining of the in the lining of the small intestines (small intestines (gut-associated lymphoid tissue or gut-associated lymphoid tissue or GALTGALT) )

bull The lymphoid tissue found beneath the mucous The lymphoid tissue found beneath the mucous membranes of the bronchi (membranes of the bronchi (bronchial-associated bronchial-associated lymphoid tissue or BALTlymphoid tissue or BALT) )

bull The lymphatic tissue found in the mucous The lymphatic tissue found in the mucous membranes (membranes (mucosa-associated lymphoid tissue or mucosa-associated lymphoid tissue or MALTMALT))

bull The lymphatic tissue found beneath the skin (The lymphatic tissue found beneath the skin (skin-skin-associated lymphoid tissue or SALTassociated lymphoid tissue or SALT) )

Primary and SecondaryPrimary and Secondary Lymphoid organs Lymphoid organs

Primarycentral lymphoid Primarycentral lymphoid organs organs

BONE MARROWBONE MARROW is a central organ is a central organ where all the immune cells are where all the immune cells are born and only B cells mature born and only B cells mature (process termed as (process termed as B B lymphopoiesis) lymphopoiesis)

THYMUSTHYMUS is the other central organ is the other central organ in which T cells mature (in which T cells mature (T T lymphopoiesislymphopoiesis) )

The bone marrowThe bone marrow

Bone marrow is a spongy tissue found Bone marrow is a spongy tissue found within boneswithin bonesAll blood cells are produced within the bone All blood cells are produced within the bone marrowmarrowThe bone marrow of an adult produce about The bone marrow of an adult produce about three million red blood cells and 120000 three million red blood cells and 120000 white blood cells every second white blood cells every second All these cells originate from a small All these cells originate from a small population of stem cells which may be as population of stem cells which may be as few as one in a million of the bone marrow few as one in a million of the bone marrow cells cells

ThymuThymuss

bullThe thymus is an organ located in the The thymus is an organ located in the upper chestupper chest bullImmature lymphocytes leave the bone Immature lymphocytes leave the bone marrow and find their way to the thymus marrow and find their way to the thymus where they are ldquoeducatedrdquo to become where they are ldquoeducatedrdquo to become mature T-lymphocytesmature T-lymphocytes

ThymusThymusFlat bilobed organ situated above the heart Flat bilobed organ situated above the heart

and below the thyroid glandand below the thyroid gland Each lobe is surrounded by a capsule and is Each lobe is surrounded by a capsule and is

divided into lobules divided into lobules The lobules are separated from each other by The lobules are separated from each other by

strands of connective tissue called strands of connective tissue called trabeculaetrabeculae

Each lobule is organized into two Each lobule is organized into two compartments the compartments the cortex cortex (outer (outer compartment) the compartment) the medullamedulla (inner (inner compartment) compartment)

bull Cortex and Medulla are both crisscrossed by Cortex and Medulla are both crisscrossed by a a network of stromal cellsnetwork of stromal cells composed of composed of

bull loosely packed thymic epithelial cells loosely packed thymic epithelial cells bull interdigitating dendritic cells interdigitating dendritic cells bull macrophages macrophages

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 23: Functional organization of the Immune System

Active and Passive Acquired Active and Passive Acquired ImmunityImmunity

bull Active immunityActive immunity

ndash Conferred by recovery from infectious diseaseConferred by recovery from infectious disease

ndash Depends on persons own immune systemDepends on persons own immune system

ndash May be acquired artificially with May be acquired artificially with vaccinesvaccines

bull Passive immunityPassive immunity

ndash transferred from person to person through transfer of antibodiestransferred from person to person through transfer of antibodies

ndash Natural instances include antibodies passing across placenta from Natural instances include antibodies passing across placenta from mother to fetus (provides temporary protection) or through the mother to fetus (provides temporary protection) or through the milkmilk

ndash Transferred artificially Eg antibody injections for rabies anti Transferred artificially Eg antibody injections for rabies anti rhesus factor snake venom botulinun toxinrhesus factor snake venom botulinun toxin

bull Lymphatic vessels are responsible for flow of lymph Lymphatic vessels are responsible for flow of lymph within the lymphoid system within the lymphoid system

bull Plasma constantly leaks out of capillaries to deliver Plasma constantly leaks out of capillaries to deliver oxygen and nutrients to cells of the surrounding oxygen and nutrients to cells of the surrounding tissue Once in the tissue the plasma is now called tissue Once in the tissue the plasma is now called tissue fluidtissue fluid

bull While most of this tissue fluid re-enters capillaries While most of this tissue fluid re-enters capillaries and is returned directly to the bloodstream some and is returned directly to the bloodstream some fluid enters lymph vessels as fluid enters lymph vessels as lymph lymph

bull LYMPH-LYMPH- flows from the intercellular tissue spaces flows from the intercellular tissue spaces into lymphatic capillaries and then into a series of into lymphatic capillaries and then into a series of larger collecting vessels called larger collecting vessels called lymphatic vesselslymphatic vessels Lymphatic vessels converge into Lymphatic vessels converge into the thoracic ductthe thoracic duct which returns the fluid to the circulatory system by which returns the fluid to the circulatory system by dumping into the left dumping into the left subclavian vein subclavian vein

Thoracicduct

Overview of blood and lymph system and how Overview of blood and lymph system and how leukocytes travel from one system to anotherleukocytes travel from one system to another

Site of exchange between theblood and lymph systems

Lymph carrying antibodiesand immune cells collect in thoracic duct where the lymph empties back into the blood circulatory system

Immune cells travel back and forth from Immune cells travel back and forth from the blood and lymph circulatory systems the blood and lymph circulatory systems and interact with extra-vascular tissues and interact with extra-vascular tissues

in the process--in the process--extravasationextravasation

muscle

Lymphatic vessels Lymphatic vessels

The organs of the The organs of the immune system immune system

Kinds of lymphoid Kinds of lymphoid OrgansOrgans

Primarycentral lymphoid organsPrimarycentral lymphoid organs ndash bone marrow bone marrow ndash thymus thymus

Secondary peripheral lymphoid tissueSecondary peripheral lymphoid tissuendash lymph nodes lymph nodes ndash spleenspleenndash mucosa-associated lymphoid tissuemucosa-associated lymphoid tissue

Kinds of Lymphoid Organs Kinds of Lymphoid Organs The Lymphoid

Organs

Primary or Central organs

Secondary or Peripheral organs

1Bone marrow2Thymus gland3Bursa of fabricius

1Lymp nodes 2Spleen

3Diffuse lymphoid tissues

bull The The bone marrowbone marrow and the and the thymusthymus constitute constitute the primary lymphoid organsthe primary lymphoid organs

bull Both Both B-lymphocytesB-lymphocytes and and T-lymphocytesT-lymphocytes are are produced from stem cells in the bone produced from stem cells in the bone marrow marrow B-lymphocytes mature in the B-lymphocytes mature in the bone marrow while T-lymphocytes bone marrow while T-lymphocytes migrate to the thymus and mature migrate to the thymus and mature therethere

bull After maturation both B-lymphocytes and T-After maturation both B-lymphocytes and T-lymphocytes circulate through and lymphocytes circulate through and accumulate in accumulate in secondary lymphoid organssecondary lymphoid organs

bull The secondary lymphoid organs include lymph nodes The secondary lymphoid organs include lymph nodes and the spleen as well as lymphoid tissues and the spleen as well as lymphoid tissues

bull The lymphoid tissues include The lymphoid tissues include the tonsils the the tonsils the appendix the Peyers patchesappendix the Peyers patches in the lining of the in the lining of the small intestines (small intestines (gut-associated lymphoid tissue or gut-associated lymphoid tissue or GALTGALT) )

bull The lymphoid tissue found beneath the mucous The lymphoid tissue found beneath the mucous membranes of the bronchi (membranes of the bronchi (bronchial-associated bronchial-associated lymphoid tissue or BALTlymphoid tissue or BALT) )

bull The lymphatic tissue found in the mucous The lymphatic tissue found in the mucous membranes (membranes (mucosa-associated lymphoid tissue or mucosa-associated lymphoid tissue or MALTMALT))

bull The lymphatic tissue found beneath the skin (The lymphatic tissue found beneath the skin (skin-skin-associated lymphoid tissue or SALTassociated lymphoid tissue or SALT) )

Primary and SecondaryPrimary and Secondary Lymphoid organs Lymphoid organs

Primarycentral lymphoid Primarycentral lymphoid organs organs

BONE MARROWBONE MARROW is a central organ is a central organ where all the immune cells are where all the immune cells are born and only B cells mature born and only B cells mature (process termed as (process termed as B B lymphopoiesis) lymphopoiesis)

THYMUSTHYMUS is the other central organ is the other central organ in which T cells mature (in which T cells mature (T T lymphopoiesislymphopoiesis) )

The bone marrowThe bone marrow

Bone marrow is a spongy tissue found Bone marrow is a spongy tissue found within boneswithin bonesAll blood cells are produced within the bone All blood cells are produced within the bone marrowmarrowThe bone marrow of an adult produce about The bone marrow of an adult produce about three million red blood cells and 120000 three million red blood cells and 120000 white blood cells every second white blood cells every second All these cells originate from a small All these cells originate from a small population of stem cells which may be as population of stem cells which may be as few as one in a million of the bone marrow few as one in a million of the bone marrow cells cells

ThymuThymuss

bullThe thymus is an organ located in the The thymus is an organ located in the upper chestupper chest bullImmature lymphocytes leave the bone Immature lymphocytes leave the bone marrow and find their way to the thymus marrow and find their way to the thymus where they are ldquoeducatedrdquo to become where they are ldquoeducatedrdquo to become mature T-lymphocytesmature T-lymphocytes

ThymusThymusFlat bilobed organ situated above the heart Flat bilobed organ situated above the heart

and below the thyroid glandand below the thyroid gland Each lobe is surrounded by a capsule and is Each lobe is surrounded by a capsule and is

divided into lobules divided into lobules The lobules are separated from each other by The lobules are separated from each other by

strands of connective tissue called strands of connective tissue called trabeculaetrabeculae

Each lobule is organized into two Each lobule is organized into two compartments the compartments the cortex cortex (outer (outer compartment) the compartment) the medullamedulla (inner (inner compartment) compartment)

bull Cortex and Medulla are both crisscrossed by Cortex and Medulla are both crisscrossed by a a network of stromal cellsnetwork of stromal cells composed of composed of

bull loosely packed thymic epithelial cells loosely packed thymic epithelial cells bull interdigitating dendritic cells interdigitating dendritic cells bull macrophages macrophages

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 24: Functional organization of the Immune System

bull Lymphatic vessels are responsible for flow of lymph Lymphatic vessels are responsible for flow of lymph within the lymphoid system within the lymphoid system

bull Plasma constantly leaks out of capillaries to deliver Plasma constantly leaks out of capillaries to deliver oxygen and nutrients to cells of the surrounding oxygen and nutrients to cells of the surrounding tissue Once in the tissue the plasma is now called tissue Once in the tissue the plasma is now called tissue fluidtissue fluid

bull While most of this tissue fluid re-enters capillaries While most of this tissue fluid re-enters capillaries and is returned directly to the bloodstream some and is returned directly to the bloodstream some fluid enters lymph vessels as fluid enters lymph vessels as lymph lymph

bull LYMPH-LYMPH- flows from the intercellular tissue spaces flows from the intercellular tissue spaces into lymphatic capillaries and then into a series of into lymphatic capillaries and then into a series of larger collecting vessels called larger collecting vessels called lymphatic vesselslymphatic vessels Lymphatic vessels converge into Lymphatic vessels converge into the thoracic ductthe thoracic duct which returns the fluid to the circulatory system by which returns the fluid to the circulatory system by dumping into the left dumping into the left subclavian vein subclavian vein

Thoracicduct

Overview of blood and lymph system and how Overview of blood and lymph system and how leukocytes travel from one system to anotherleukocytes travel from one system to another

Site of exchange between theblood and lymph systems

Lymph carrying antibodiesand immune cells collect in thoracic duct where the lymph empties back into the blood circulatory system

Immune cells travel back and forth from Immune cells travel back and forth from the blood and lymph circulatory systems the blood and lymph circulatory systems and interact with extra-vascular tissues and interact with extra-vascular tissues

in the process--in the process--extravasationextravasation

muscle

Lymphatic vessels Lymphatic vessels

The organs of the The organs of the immune system immune system

Kinds of lymphoid Kinds of lymphoid OrgansOrgans

Primarycentral lymphoid organsPrimarycentral lymphoid organs ndash bone marrow bone marrow ndash thymus thymus

Secondary peripheral lymphoid tissueSecondary peripheral lymphoid tissuendash lymph nodes lymph nodes ndash spleenspleenndash mucosa-associated lymphoid tissuemucosa-associated lymphoid tissue

Kinds of Lymphoid Organs Kinds of Lymphoid Organs The Lymphoid

Organs

Primary or Central organs

Secondary or Peripheral organs

1Bone marrow2Thymus gland3Bursa of fabricius

1Lymp nodes 2Spleen

3Diffuse lymphoid tissues

bull The The bone marrowbone marrow and the and the thymusthymus constitute constitute the primary lymphoid organsthe primary lymphoid organs

bull Both Both B-lymphocytesB-lymphocytes and and T-lymphocytesT-lymphocytes are are produced from stem cells in the bone produced from stem cells in the bone marrow marrow B-lymphocytes mature in the B-lymphocytes mature in the bone marrow while T-lymphocytes bone marrow while T-lymphocytes migrate to the thymus and mature migrate to the thymus and mature therethere

bull After maturation both B-lymphocytes and T-After maturation both B-lymphocytes and T-lymphocytes circulate through and lymphocytes circulate through and accumulate in accumulate in secondary lymphoid organssecondary lymphoid organs

bull The secondary lymphoid organs include lymph nodes The secondary lymphoid organs include lymph nodes and the spleen as well as lymphoid tissues and the spleen as well as lymphoid tissues

bull The lymphoid tissues include The lymphoid tissues include the tonsils the the tonsils the appendix the Peyers patchesappendix the Peyers patches in the lining of the in the lining of the small intestines (small intestines (gut-associated lymphoid tissue or gut-associated lymphoid tissue or GALTGALT) )

bull The lymphoid tissue found beneath the mucous The lymphoid tissue found beneath the mucous membranes of the bronchi (membranes of the bronchi (bronchial-associated bronchial-associated lymphoid tissue or BALTlymphoid tissue or BALT) )

bull The lymphatic tissue found in the mucous The lymphatic tissue found in the mucous membranes (membranes (mucosa-associated lymphoid tissue or mucosa-associated lymphoid tissue or MALTMALT))

bull The lymphatic tissue found beneath the skin (The lymphatic tissue found beneath the skin (skin-skin-associated lymphoid tissue or SALTassociated lymphoid tissue or SALT) )

Primary and SecondaryPrimary and Secondary Lymphoid organs Lymphoid organs

Primarycentral lymphoid Primarycentral lymphoid organs organs

BONE MARROWBONE MARROW is a central organ is a central organ where all the immune cells are where all the immune cells are born and only B cells mature born and only B cells mature (process termed as (process termed as B B lymphopoiesis) lymphopoiesis)

THYMUSTHYMUS is the other central organ is the other central organ in which T cells mature (in which T cells mature (T T lymphopoiesislymphopoiesis) )

The bone marrowThe bone marrow

Bone marrow is a spongy tissue found Bone marrow is a spongy tissue found within boneswithin bonesAll blood cells are produced within the bone All blood cells are produced within the bone marrowmarrowThe bone marrow of an adult produce about The bone marrow of an adult produce about three million red blood cells and 120000 three million red blood cells and 120000 white blood cells every second white blood cells every second All these cells originate from a small All these cells originate from a small population of stem cells which may be as population of stem cells which may be as few as one in a million of the bone marrow few as one in a million of the bone marrow cells cells

ThymuThymuss

bullThe thymus is an organ located in the The thymus is an organ located in the upper chestupper chest bullImmature lymphocytes leave the bone Immature lymphocytes leave the bone marrow and find their way to the thymus marrow and find their way to the thymus where they are ldquoeducatedrdquo to become where they are ldquoeducatedrdquo to become mature T-lymphocytesmature T-lymphocytes

ThymusThymusFlat bilobed organ situated above the heart Flat bilobed organ situated above the heart

and below the thyroid glandand below the thyroid gland Each lobe is surrounded by a capsule and is Each lobe is surrounded by a capsule and is

divided into lobules divided into lobules The lobules are separated from each other by The lobules are separated from each other by

strands of connective tissue called strands of connective tissue called trabeculaetrabeculae

Each lobule is organized into two Each lobule is organized into two compartments the compartments the cortex cortex (outer (outer compartment) the compartment) the medullamedulla (inner (inner compartment) compartment)

bull Cortex and Medulla are both crisscrossed by Cortex and Medulla are both crisscrossed by a a network of stromal cellsnetwork of stromal cells composed of composed of

bull loosely packed thymic epithelial cells loosely packed thymic epithelial cells bull interdigitating dendritic cells interdigitating dendritic cells bull macrophages macrophages

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 25: Functional organization of the Immune System

Thoracicduct

Overview of blood and lymph system and how Overview of blood and lymph system and how leukocytes travel from one system to anotherleukocytes travel from one system to another

Site of exchange between theblood and lymph systems

Lymph carrying antibodiesand immune cells collect in thoracic duct where the lymph empties back into the blood circulatory system

Immune cells travel back and forth from Immune cells travel back and forth from the blood and lymph circulatory systems the blood and lymph circulatory systems and interact with extra-vascular tissues and interact with extra-vascular tissues

in the process--in the process--extravasationextravasation

muscle

Lymphatic vessels Lymphatic vessels

The organs of the The organs of the immune system immune system

Kinds of lymphoid Kinds of lymphoid OrgansOrgans

Primarycentral lymphoid organsPrimarycentral lymphoid organs ndash bone marrow bone marrow ndash thymus thymus

Secondary peripheral lymphoid tissueSecondary peripheral lymphoid tissuendash lymph nodes lymph nodes ndash spleenspleenndash mucosa-associated lymphoid tissuemucosa-associated lymphoid tissue

Kinds of Lymphoid Organs Kinds of Lymphoid Organs The Lymphoid

Organs

Primary or Central organs

Secondary or Peripheral organs

1Bone marrow2Thymus gland3Bursa of fabricius

1Lymp nodes 2Spleen

3Diffuse lymphoid tissues

bull The The bone marrowbone marrow and the and the thymusthymus constitute constitute the primary lymphoid organsthe primary lymphoid organs

bull Both Both B-lymphocytesB-lymphocytes and and T-lymphocytesT-lymphocytes are are produced from stem cells in the bone produced from stem cells in the bone marrow marrow B-lymphocytes mature in the B-lymphocytes mature in the bone marrow while T-lymphocytes bone marrow while T-lymphocytes migrate to the thymus and mature migrate to the thymus and mature therethere

bull After maturation both B-lymphocytes and T-After maturation both B-lymphocytes and T-lymphocytes circulate through and lymphocytes circulate through and accumulate in accumulate in secondary lymphoid organssecondary lymphoid organs

bull The secondary lymphoid organs include lymph nodes The secondary lymphoid organs include lymph nodes and the spleen as well as lymphoid tissues and the spleen as well as lymphoid tissues

bull The lymphoid tissues include The lymphoid tissues include the tonsils the the tonsils the appendix the Peyers patchesappendix the Peyers patches in the lining of the in the lining of the small intestines (small intestines (gut-associated lymphoid tissue or gut-associated lymphoid tissue or GALTGALT) )

bull The lymphoid tissue found beneath the mucous The lymphoid tissue found beneath the mucous membranes of the bronchi (membranes of the bronchi (bronchial-associated bronchial-associated lymphoid tissue or BALTlymphoid tissue or BALT) )

bull The lymphatic tissue found in the mucous The lymphatic tissue found in the mucous membranes (membranes (mucosa-associated lymphoid tissue or mucosa-associated lymphoid tissue or MALTMALT))

bull The lymphatic tissue found beneath the skin (The lymphatic tissue found beneath the skin (skin-skin-associated lymphoid tissue or SALTassociated lymphoid tissue or SALT) )

Primary and SecondaryPrimary and Secondary Lymphoid organs Lymphoid organs

Primarycentral lymphoid Primarycentral lymphoid organs organs

BONE MARROWBONE MARROW is a central organ is a central organ where all the immune cells are where all the immune cells are born and only B cells mature born and only B cells mature (process termed as (process termed as B B lymphopoiesis) lymphopoiesis)

THYMUSTHYMUS is the other central organ is the other central organ in which T cells mature (in which T cells mature (T T lymphopoiesislymphopoiesis) )

The bone marrowThe bone marrow

Bone marrow is a spongy tissue found Bone marrow is a spongy tissue found within boneswithin bonesAll blood cells are produced within the bone All blood cells are produced within the bone marrowmarrowThe bone marrow of an adult produce about The bone marrow of an adult produce about three million red blood cells and 120000 three million red blood cells and 120000 white blood cells every second white blood cells every second All these cells originate from a small All these cells originate from a small population of stem cells which may be as population of stem cells which may be as few as one in a million of the bone marrow few as one in a million of the bone marrow cells cells

ThymuThymuss

bullThe thymus is an organ located in the The thymus is an organ located in the upper chestupper chest bullImmature lymphocytes leave the bone Immature lymphocytes leave the bone marrow and find their way to the thymus marrow and find their way to the thymus where they are ldquoeducatedrdquo to become where they are ldquoeducatedrdquo to become mature T-lymphocytesmature T-lymphocytes

ThymusThymusFlat bilobed organ situated above the heart Flat bilobed organ situated above the heart

and below the thyroid glandand below the thyroid gland Each lobe is surrounded by a capsule and is Each lobe is surrounded by a capsule and is

divided into lobules divided into lobules The lobules are separated from each other by The lobules are separated from each other by

strands of connective tissue called strands of connective tissue called trabeculaetrabeculae

Each lobule is organized into two Each lobule is organized into two compartments the compartments the cortex cortex (outer (outer compartment) the compartment) the medullamedulla (inner (inner compartment) compartment)

bull Cortex and Medulla are both crisscrossed by Cortex and Medulla are both crisscrossed by a a network of stromal cellsnetwork of stromal cells composed of composed of

bull loosely packed thymic epithelial cells loosely packed thymic epithelial cells bull interdigitating dendritic cells interdigitating dendritic cells bull macrophages macrophages

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 26: Functional organization of the Immune System

Immune cells travel back and forth from Immune cells travel back and forth from the blood and lymph circulatory systems the blood and lymph circulatory systems and interact with extra-vascular tissues and interact with extra-vascular tissues

in the process--in the process--extravasationextravasation

muscle

Lymphatic vessels Lymphatic vessels

The organs of the The organs of the immune system immune system

Kinds of lymphoid Kinds of lymphoid OrgansOrgans

Primarycentral lymphoid organsPrimarycentral lymphoid organs ndash bone marrow bone marrow ndash thymus thymus

Secondary peripheral lymphoid tissueSecondary peripheral lymphoid tissuendash lymph nodes lymph nodes ndash spleenspleenndash mucosa-associated lymphoid tissuemucosa-associated lymphoid tissue

Kinds of Lymphoid Organs Kinds of Lymphoid Organs The Lymphoid

Organs

Primary or Central organs

Secondary or Peripheral organs

1Bone marrow2Thymus gland3Bursa of fabricius

1Lymp nodes 2Spleen

3Diffuse lymphoid tissues

bull The The bone marrowbone marrow and the and the thymusthymus constitute constitute the primary lymphoid organsthe primary lymphoid organs

bull Both Both B-lymphocytesB-lymphocytes and and T-lymphocytesT-lymphocytes are are produced from stem cells in the bone produced from stem cells in the bone marrow marrow B-lymphocytes mature in the B-lymphocytes mature in the bone marrow while T-lymphocytes bone marrow while T-lymphocytes migrate to the thymus and mature migrate to the thymus and mature therethere

bull After maturation both B-lymphocytes and T-After maturation both B-lymphocytes and T-lymphocytes circulate through and lymphocytes circulate through and accumulate in accumulate in secondary lymphoid organssecondary lymphoid organs

bull The secondary lymphoid organs include lymph nodes The secondary lymphoid organs include lymph nodes and the spleen as well as lymphoid tissues and the spleen as well as lymphoid tissues

bull The lymphoid tissues include The lymphoid tissues include the tonsils the the tonsils the appendix the Peyers patchesappendix the Peyers patches in the lining of the in the lining of the small intestines (small intestines (gut-associated lymphoid tissue or gut-associated lymphoid tissue or GALTGALT) )

bull The lymphoid tissue found beneath the mucous The lymphoid tissue found beneath the mucous membranes of the bronchi (membranes of the bronchi (bronchial-associated bronchial-associated lymphoid tissue or BALTlymphoid tissue or BALT) )

bull The lymphatic tissue found in the mucous The lymphatic tissue found in the mucous membranes (membranes (mucosa-associated lymphoid tissue or mucosa-associated lymphoid tissue or MALTMALT))

bull The lymphatic tissue found beneath the skin (The lymphatic tissue found beneath the skin (skin-skin-associated lymphoid tissue or SALTassociated lymphoid tissue or SALT) )

Primary and SecondaryPrimary and Secondary Lymphoid organs Lymphoid organs

Primarycentral lymphoid Primarycentral lymphoid organs organs

BONE MARROWBONE MARROW is a central organ is a central organ where all the immune cells are where all the immune cells are born and only B cells mature born and only B cells mature (process termed as (process termed as B B lymphopoiesis) lymphopoiesis)

THYMUSTHYMUS is the other central organ is the other central organ in which T cells mature (in which T cells mature (T T lymphopoiesislymphopoiesis) )

The bone marrowThe bone marrow

Bone marrow is a spongy tissue found Bone marrow is a spongy tissue found within boneswithin bonesAll blood cells are produced within the bone All blood cells are produced within the bone marrowmarrowThe bone marrow of an adult produce about The bone marrow of an adult produce about three million red blood cells and 120000 three million red blood cells and 120000 white blood cells every second white blood cells every second All these cells originate from a small All these cells originate from a small population of stem cells which may be as population of stem cells which may be as few as one in a million of the bone marrow few as one in a million of the bone marrow cells cells

ThymuThymuss

bullThe thymus is an organ located in the The thymus is an organ located in the upper chestupper chest bullImmature lymphocytes leave the bone Immature lymphocytes leave the bone marrow and find their way to the thymus marrow and find their way to the thymus where they are ldquoeducatedrdquo to become where they are ldquoeducatedrdquo to become mature T-lymphocytesmature T-lymphocytes

ThymusThymusFlat bilobed organ situated above the heart Flat bilobed organ situated above the heart

and below the thyroid glandand below the thyroid gland Each lobe is surrounded by a capsule and is Each lobe is surrounded by a capsule and is

divided into lobules divided into lobules The lobules are separated from each other by The lobules are separated from each other by

strands of connective tissue called strands of connective tissue called trabeculaetrabeculae

Each lobule is organized into two Each lobule is organized into two compartments the compartments the cortex cortex (outer (outer compartment) the compartment) the medullamedulla (inner (inner compartment) compartment)

bull Cortex and Medulla are both crisscrossed by Cortex and Medulla are both crisscrossed by a a network of stromal cellsnetwork of stromal cells composed of composed of

bull loosely packed thymic epithelial cells loosely packed thymic epithelial cells bull interdigitating dendritic cells interdigitating dendritic cells bull macrophages macrophages

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 27: Functional organization of the Immune System

Lymphatic vessels Lymphatic vessels

The organs of the The organs of the immune system immune system

Kinds of lymphoid Kinds of lymphoid OrgansOrgans

Primarycentral lymphoid organsPrimarycentral lymphoid organs ndash bone marrow bone marrow ndash thymus thymus

Secondary peripheral lymphoid tissueSecondary peripheral lymphoid tissuendash lymph nodes lymph nodes ndash spleenspleenndash mucosa-associated lymphoid tissuemucosa-associated lymphoid tissue

Kinds of Lymphoid Organs Kinds of Lymphoid Organs The Lymphoid

Organs

Primary or Central organs

Secondary or Peripheral organs

1Bone marrow2Thymus gland3Bursa of fabricius

1Lymp nodes 2Spleen

3Diffuse lymphoid tissues

bull The The bone marrowbone marrow and the and the thymusthymus constitute constitute the primary lymphoid organsthe primary lymphoid organs

bull Both Both B-lymphocytesB-lymphocytes and and T-lymphocytesT-lymphocytes are are produced from stem cells in the bone produced from stem cells in the bone marrow marrow B-lymphocytes mature in the B-lymphocytes mature in the bone marrow while T-lymphocytes bone marrow while T-lymphocytes migrate to the thymus and mature migrate to the thymus and mature therethere

bull After maturation both B-lymphocytes and T-After maturation both B-lymphocytes and T-lymphocytes circulate through and lymphocytes circulate through and accumulate in accumulate in secondary lymphoid organssecondary lymphoid organs

bull The secondary lymphoid organs include lymph nodes The secondary lymphoid organs include lymph nodes and the spleen as well as lymphoid tissues and the spleen as well as lymphoid tissues

bull The lymphoid tissues include The lymphoid tissues include the tonsils the the tonsils the appendix the Peyers patchesappendix the Peyers patches in the lining of the in the lining of the small intestines (small intestines (gut-associated lymphoid tissue or gut-associated lymphoid tissue or GALTGALT) )

bull The lymphoid tissue found beneath the mucous The lymphoid tissue found beneath the mucous membranes of the bronchi (membranes of the bronchi (bronchial-associated bronchial-associated lymphoid tissue or BALTlymphoid tissue or BALT) )

bull The lymphatic tissue found in the mucous The lymphatic tissue found in the mucous membranes (membranes (mucosa-associated lymphoid tissue or mucosa-associated lymphoid tissue or MALTMALT))

bull The lymphatic tissue found beneath the skin (The lymphatic tissue found beneath the skin (skin-skin-associated lymphoid tissue or SALTassociated lymphoid tissue or SALT) )

Primary and SecondaryPrimary and Secondary Lymphoid organs Lymphoid organs

Primarycentral lymphoid Primarycentral lymphoid organs organs

BONE MARROWBONE MARROW is a central organ is a central organ where all the immune cells are where all the immune cells are born and only B cells mature born and only B cells mature (process termed as (process termed as B B lymphopoiesis) lymphopoiesis)

THYMUSTHYMUS is the other central organ is the other central organ in which T cells mature (in which T cells mature (T T lymphopoiesislymphopoiesis) )

The bone marrowThe bone marrow

Bone marrow is a spongy tissue found Bone marrow is a spongy tissue found within boneswithin bonesAll blood cells are produced within the bone All blood cells are produced within the bone marrowmarrowThe bone marrow of an adult produce about The bone marrow of an adult produce about three million red blood cells and 120000 three million red blood cells and 120000 white blood cells every second white blood cells every second All these cells originate from a small All these cells originate from a small population of stem cells which may be as population of stem cells which may be as few as one in a million of the bone marrow few as one in a million of the bone marrow cells cells

ThymuThymuss

bullThe thymus is an organ located in the The thymus is an organ located in the upper chestupper chest bullImmature lymphocytes leave the bone Immature lymphocytes leave the bone marrow and find their way to the thymus marrow and find their way to the thymus where they are ldquoeducatedrdquo to become where they are ldquoeducatedrdquo to become mature T-lymphocytesmature T-lymphocytes

ThymusThymusFlat bilobed organ situated above the heart Flat bilobed organ situated above the heart

and below the thyroid glandand below the thyroid gland Each lobe is surrounded by a capsule and is Each lobe is surrounded by a capsule and is

divided into lobules divided into lobules The lobules are separated from each other by The lobules are separated from each other by

strands of connective tissue called strands of connective tissue called trabeculaetrabeculae

Each lobule is organized into two Each lobule is organized into two compartments the compartments the cortex cortex (outer (outer compartment) the compartment) the medullamedulla (inner (inner compartment) compartment)

bull Cortex and Medulla are both crisscrossed by Cortex and Medulla are both crisscrossed by a a network of stromal cellsnetwork of stromal cells composed of composed of

bull loosely packed thymic epithelial cells loosely packed thymic epithelial cells bull interdigitating dendritic cells interdigitating dendritic cells bull macrophages macrophages

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 28: Functional organization of the Immune System

The organs of the The organs of the immune system immune system

Kinds of lymphoid Kinds of lymphoid OrgansOrgans

Primarycentral lymphoid organsPrimarycentral lymphoid organs ndash bone marrow bone marrow ndash thymus thymus

Secondary peripheral lymphoid tissueSecondary peripheral lymphoid tissuendash lymph nodes lymph nodes ndash spleenspleenndash mucosa-associated lymphoid tissuemucosa-associated lymphoid tissue

Kinds of Lymphoid Organs Kinds of Lymphoid Organs The Lymphoid

Organs

Primary or Central organs

Secondary or Peripheral organs

1Bone marrow2Thymus gland3Bursa of fabricius

1Lymp nodes 2Spleen

3Diffuse lymphoid tissues

bull The The bone marrowbone marrow and the and the thymusthymus constitute constitute the primary lymphoid organsthe primary lymphoid organs

bull Both Both B-lymphocytesB-lymphocytes and and T-lymphocytesT-lymphocytes are are produced from stem cells in the bone produced from stem cells in the bone marrow marrow B-lymphocytes mature in the B-lymphocytes mature in the bone marrow while T-lymphocytes bone marrow while T-lymphocytes migrate to the thymus and mature migrate to the thymus and mature therethere

bull After maturation both B-lymphocytes and T-After maturation both B-lymphocytes and T-lymphocytes circulate through and lymphocytes circulate through and accumulate in accumulate in secondary lymphoid organssecondary lymphoid organs

bull The secondary lymphoid organs include lymph nodes The secondary lymphoid organs include lymph nodes and the spleen as well as lymphoid tissues and the spleen as well as lymphoid tissues

bull The lymphoid tissues include The lymphoid tissues include the tonsils the the tonsils the appendix the Peyers patchesappendix the Peyers patches in the lining of the in the lining of the small intestines (small intestines (gut-associated lymphoid tissue or gut-associated lymphoid tissue or GALTGALT) )

bull The lymphoid tissue found beneath the mucous The lymphoid tissue found beneath the mucous membranes of the bronchi (membranes of the bronchi (bronchial-associated bronchial-associated lymphoid tissue or BALTlymphoid tissue or BALT) )

bull The lymphatic tissue found in the mucous The lymphatic tissue found in the mucous membranes (membranes (mucosa-associated lymphoid tissue or mucosa-associated lymphoid tissue or MALTMALT))

bull The lymphatic tissue found beneath the skin (The lymphatic tissue found beneath the skin (skin-skin-associated lymphoid tissue or SALTassociated lymphoid tissue or SALT) )

Primary and SecondaryPrimary and Secondary Lymphoid organs Lymphoid organs

Primarycentral lymphoid Primarycentral lymphoid organs organs

BONE MARROWBONE MARROW is a central organ is a central organ where all the immune cells are where all the immune cells are born and only B cells mature born and only B cells mature (process termed as (process termed as B B lymphopoiesis) lymphopoiesis)

THYMUSTHYMUS is the other central organ is the other central organ in which T cells mature (in which T cells mature (T T lymphopoiesislymphopoiesis) )

The bone marrowThe bone marrow

Bone marrow is a spongy tissue found Bone marrow is a spongy tissue found within boneswithin bonesAll blood cells are produced within the bone All blood cells are produced within the bone marrowmarrowThe bone marrow of an adult produce about The bone marrow of an adult produce about three million red blood cells and 120000 three million red blood cells and 120000 white blood cells every second white blood cells every second All these cells originate from a small All these cells originate from a small population of stem cells which may be as population of stem cells which may be as few as one in a million of the bone marrow few as one in a million of the bone marrow cells cells

ThymuThymuss

bullThe thymus is an organ located in the The thymus is an organ located in the upper chestupper chest bullImmature lymphocytes leave the bone Immature lymphocytes leave the bone marrow and find their way to the thymus marrow and find their way to the thymus where they are ldquoeducatedrdquo to become where they are ldquoeducatedrdquo to become mature T-lymphocytesmature T-lymphocytes

ThymusThymusFlat bilobed organ situated above the heart Flat bilobed organ situated above the heart

and below the thyroid glandand below the thyroid gland Each lobe is surrounded by a capsule and is Each lobe is surrounded by a capsule and is

divided into lobules divided into lobules The lobules are separated from each other by The lobules are separated from each other by

strands of connective tissue called strands of connective tissue called trabeculaetrabeculae

Each lobule is organized into two Each lobule is organized into two compartments the compartments the cortex cortex (outer (outer compartment) the compartment) the medullamedulla (inner (inner compartment) compartment)

bull Cortex and Medulla are both crisscrossed by Cortex and Medulla are both crisscrossed by a a network of stromal cellsnetwork of stromal cells composed of composed of

bull loosely packed thymic epithelial cells loosely packed thymic epithelial cells bull interdigitating dendritic cells interdigitating dendritic cells bull macrophages macrophages

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 29: Functional organization of the Immune System

Kinds of lymphoid Kinds of lymphoid OrgansOrgans

Primarycentral lymphoid organsPrimarycentral lymphoid organs ndash bone marrow bone marrow ndash thymus thymus

Secondary peripheral lymphoid tissueSecondary peripheral lymphoid tissuendash lymph nodes lymph nodes ndash spleenspleenndash mucosa-associated lymphoid tissuemucosa-associated lymphoid tissue

Kinds of Lymphoid Organs Kinds of Lymphoid Organs The Lymphoid

Organs

Primary or Central organs

Secondary or Peripheral organs

1Bone marrow2Thymus gland3Bursa of fabricius

1Lymp nodes 2Spleen

3Diffuse lymphoid tissues

bull The The bone marrowbone marrow and the and the thymusthymus constitute constitute the primary lymphoid organsthe primary lymphoid organs

bull Both Both B-lymphocytesB-lymphocytes and and T-lymphocytesT-lymphocytes are are produced from stem cells in the bone produced from stem cells in the bone marrow marrow B-lymphocytes mature in the B-lymphocytes mature in the bone marrow while T-lymphocytes bone marrow while T-lymphocytes migrate to the thymus and mature migrate to the thymus and mature therethere

bull After maturation both B-lymphocytes and T-After maturation both B-lymphocytes and T-lymphocytes circulate through and lymphocytes circulate through and accumulate in accumulate in secondary lymphoid organssecondary lymphoid organs

bull The secondary lymphoid organs include lymph nodes The secondary lymphoid organs include lymph nodes and the spleen as well as lymphoid tissues and the spleen as well as lymphoid tissues

bull The lymphoid tissues include The lymphoid tissues include the tonsils the the tonsils the appendix the Peyers patchesappendix the Peyers patches in the lining of the in the lining of the small intestines (small intestines (gut-associated lymphoid tissue or gut-associated lymphoid tissue or GALTGALT) )

bull The lymphoid tissue found beneath the mucous The lymphoid tissue found beneath the mucous membranes of the bronchi (membranes of the bronchi (bronchial-associated bronchial-associated lymphoid tissue or BALTlymphoid tissue or BALT) )

bull The lymphatic tissue found in the mucous The lymphatic tissue found in the mucous membranes (membranes (mucosa-associated lymphoid tissue or mucosa-associated lymphoid tissue or MALTMALT))

bull The lymphatic tissue found beneath the skin (The lymphatic tissue found beneath the skin (skin-skin-associated lymphoid tissue or SALTassociated lymphoid tissue or SALT) )

Primary and SecondaryPrimary and Secondary Lymphoid organs Lymphoid organs

Primarycentral lymphoid Primarycentral lymphoid organs organs

BONE MARROWBONE MARROW is a central organ is a central organ where all the immune cells are where all the immune cells are born and only B cells mature born and only B cells mature (process termed as (process termed as B B lymphopoiesis) lymphopoiesis)

THYMUSTHYMUS is the other central organ is the other central organ in which T cells mature (in which T cells mature (T T lymphopoiesislymphopoiesis) )

The bone marrowThe bone marrow

Bone marrow is a spongy tissue found Bone marrow is a spongy tissue found within boneswithin bonesAll blood cells are produced within the bone All blood cells are produced within the bone marrowmarrowThe bone marrow of an adult produce about The bone marrow of an adult produce about three million red blood cells and 120000 three million red blood cells and 120000 white blood cells every second white blood cells every second All these cells originate from a small All these cells originate from a small population of stem cells which may be as population of stem cells which may be as few as one in a million of the bone marrow few as one in a million of the bone marrow cells cells

ThymuThymuss

bullThe thymus is an organ located in the The thymus is an organ located in the upper chestupper chest bullImmature lymphocytes leave the bone Immature lymphocytes leave the bone marrow and find their way to the thymus marrow and find their way to the thymus where they are ldquoeducatedrdquo to become where they are ldquoeducatedrdquo to become mature T-lymphocytesmature T-lymphocytes

ThymusThymusFlat bilobed organ situated above the heart Flat bilobed organ situated above the heart

and below the thyroid glandand below the thyroid gland Each lobe is surrounded by a capsule and is Each lobe is surrounded by a capsule and is

divided into lobules divided into lobules The lobules are separated from each other by The lobules are separated from each other by

strands of connective tissue called strands of connective tissue called trabeculaetrabeculae

Each lobule is organized into two Each lobule is organized into two compartments the compartments the cortex cortex (outer (outer compartment) the compartment) the medullamedulla (inner (inner compartment) compartment)

bull Cortex and Medulla are both crisscrossed by Cortex and Medulla are both crisscrossed by a a network of stromal cellsnetwork of stromal cells composed of composed of

bull loosely packed thymic epithelial cells loosely packed thymic epithelial cells bull interdigitating dendritic cells interdigitating dendritic cells bull macrophages macrophages

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 30: Functional organization of the Immune System

Kinds of Lymphoid Organs Kinds of Lymphoid Organs The Lymphoid

Organs

Primary or Central organs

Secondary or Peripheral organs

1Bone marrow2Thymus gland3Bursa of fabricius

1Lymp nodes 2Spleen

3Diffuse lymphoid tissues

bull The The bone marrowbone marrow and the and the thymusthymus constitute constitute the primary lymphoid organsthe primary lymphoid organs

bull Both Both B-lymphocytesB-lymphocytes and and T-lymphocytesT-lymphocytes are are produced from stem cells in the bone produced from stem cells in the bone marrow marrow B-lymphocytes mature in the B-lymphocytes mature in the bone marrow while T-lymphocytes bone marrow while T-lymphocytes migrate to the thymus and mature migrate to the thymus and mature therethere

bull After maturation both B-lymphocytes and T-After maturation both B-lymphocytes and T-lymphocytes circulate through and lymphocytes circulate through and accumulate in accumulate in secondary lymphoid organssecondary lymphoid organs

bull The secondary lymphoid organs include lymph nodes The secondary lymphoid organs include lymph nodes and the spleen as well as lymphoid tissues and the spleen as well as lymphoid tissues

bull The lymphoid tissues include The lymphoid tissues include the tonsils the the tonsils the appendix the Peyers patchesappendix the Peyers patches in the lining of the in the lining of the small intestines (small intestines (gut-associated lymphoid tissue or gut-associated lymphoid tissue or GALTGALT) )

bull The lymphoid tissue found beneath the mucous The lymphoid tissue found beneath the mucous membranes of the bronchi (membranes of the bronchi (bronchial-associated bronchial-associated lymphoid tissue or BALTlymphoid tissue or BALT) )

bull The lymphatic tissue found in the mucous The lymphatic tissue found in the mucous membranes (membranes (mucosa-associated lymphoid tissue or mucosa-associated lymphoid tissue or MALTMALT))

bull The lymphatic tissue found beneath the skin (The lymphatic tissue found beneath the skin (skin-skin-associated lymphoid tissue or SALTassociated lymphoid tissue or SALT) )

Primary and SecondaryPrimary and Secondary Lymphoid organs Lymphoid organs

Primarycentral lymphoid Primarycentral lymphoid organs organs

BONE MARROWBONE MARROW is a central organ is a central organ where all the immune cells are where all the immune cells are born and only B cells mature born and only B cells mature (process termed as (process termed as B B lymphopoiesis) lymphopoiesis)

THYMUSTHYMUS is the other central organ is the other central organ in which T cells mature (in which T cells mature (T T lymphopoiesislymphopoiesis) )

The bone marrowThe bone marrow

Bone marrow is a spongy tissue found Bone marrow is a spongy tissue found within boneswithin bonesAll blood cells are produced within the bone All blood cells are produced within the bone marrowmarrowThe bone marrow of an adult produce about The bone marrow of an adult produce about three million red blood cells and 120000 three million red blood cells and 120000 white blood cells every second white blood cells every second All these cells originate from a small All these cells originate from a small population of stem cells which may be as population of stem cells which may be as few as one in a million of the bone marrow few as one in a million of the bone marrow cells cells

ThymuThymuss

bullThe thymus is an organ located in the The thymus is an organ located in the upper chestupper chest bullImmature lymphocytes leave the bone Immature lymphocytes leave the bone marrow and find their way to the thymus marrow and find their way to the thymus where they are ldquoeducatedrdquo to become where they are ldquoeducatedrdquo to become mature T-lymphocytesmature T-lymphocytes

ThymusThymusFlat bilobed organ situated above the heart Flat bilobed organ situated above the heart

and below the thyroid glandand below the thyroid gland Each lobe is surrounded by a capsule and is Each lobe is surrounded by a capsule and is

divided into lobules divided into lobules The lobules are separated from each other by The lobules are separated from each other by

strands of connective tissue called strands of connective tissue called trabeculaetrabeculae

Each lobule is organized into two Each lobule is organized into two compartments the compartments the cortex cortex (outer (outer compartment) the compartment) the medullamedulla (inner (inner compartment) compartment)

bull Cortex and Medulla are both crisscrossed by Cortex and Medulla are both crisscrossed by a a network of stromal cellsnetwork of stromal cells composed of composed of

bull loosely packed thymic epithelial cells loosely packed thymic epithelial cells bull interdigitating dendritic cells interdigitating dendritic cells bull macrophages macrophages

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 31: Functional organization of the Immune System

bull The The bone marrowbone marrow and the and the thymusthymus constitute constitute the primary lymphoid organsthe primary lymphoid organs

bull Both Both B-lymphocytesB-lymphocytes and and T-lymphocytesT-lymphocytes are are produced from stem cells in the bone produced from stem cells in the bone marrow marrow B-lymphocytes mature in the B-lymphocytes mature in the bone marrow while T-lymphocytes bone marrow while T-lymphocytes migrate to the thymus and mature migrate to the thymus and mature therethere

bull After maturation both B-lymphocytes and T-After maturation both B-lymphocytes and T-lymphocytes circulate through and lymphocytes circulate through and accumulate in accumulate in secondary lymphoid organssecondary lymphoid organs

bull The secondary lymphoid organs include lymph nodes The secondary lymphoid organs include lymph nodes and the spleen as well as lymphoid tissues and the spleen as well as lymphoid tissues

bull The lymphoid tissues include The lymphoid tissues include the tonsils the the tonsils the appendix the Peyers patchesappendix the Peyers patches in the lining of the in the lining of the small intestines (small intestines (gut-associated lymphoid tissue or gut-associated lymphoid tissue or GALTGALT) )

bull The lymphoid tissue found beneath the mucous The lymphoid tissue found beneath the mucous membranes of the bronchi (membranes of the bronchi (bronchial-associated bronchial-associated lymphoid tissue or BALTlymphoid tissue or BALT) )

bull The lymphatic tissue found in the mucous The lymphatic tissue found in the mucous membranes (membranes (mucosa-associated lymphoid tissue or mucosa-associated lymphoid tissue or MALTMALT))

bull The lymphatic tissue found beneath the skin (The lymphatic tissue found beneath the skin (skin-skin-associated lymphoid tissue or SALTassociated lymphoid tissue or SALT) )

Primary and SecondaryPrimary and Secondary Lymphoid organs Lymphoid organs

Primarycentral lymphoid Primarycentral lymphoid organs organs

BONE MARROWBONE MARROW is a central organ is a central organ where all the immune cells are where all the immune cells are born and only B cells mature born and only B cells mature (process termed as (process termed as B B lymphopoiesis) lymphopoiesis)

THYMUSTHYMUS is the other central organ is the other central organ in which T cells mature (in which T cells mature (T T lymphopoiesislymphopoiesis) )

The bone marrowThe bone marrow

Bone marrow is a spongy tissue found Bone marrow is a spongy tissue found within boneswithin bonesAll blood cells are produced within the bone All blood cells are produced within the bone marrowmarrowThe bone marrow of an adult produce about The bone marrow of an adult produce about three million red blood cells and 120000 three million red blood cells and 120000 white blood cells every second white blood cells every second All these cells originate from a small All these cells originate from a small population of stem cells which may be as population of stem cells which may be as few as one in a million of the bone marrow few as one in a million of the bone marrow cells cells

ThymuThymuss

bullThe thymus is an organ located in the The thymus is an organ located in the upper chestupper chest bullImmature lymphocytes leave the bone Immature lymphocytes leave the bone marrow and find their way to the thymus marrow and find their way to the thymus where they are ldquoeducatedrdquo to become where they are ldquoeducatedrdquo to become mature T-lymphocytesmature T-lymphocytes

ThymusThymusFlat bilobed organ situated above the heart Flat bilobed organ situated above the heart

and below the thyroid glandand below the thyroid gland Each lobe is surrounded by a capsule and is Each lobe is surrounded by a capsule and is

divided into lobules divided into lobules The lobules are separated from each other by The lobules are separated from each other by

strands of connective tissue called strands of connective tissue called trabeculaetrabeculae

Each lobule is organized into two Each lobule is organized into two compartments the compartments the cortex cortex (outer (outer compartment) the compartment) the medullamedulla (inner (inner compartment) compartment)

bull Cortex and Medulla are both crisscrossed by Cortex and Medulla are both crisscrossed by a a network of stromal cellsnetwork of stromal cells composed of composed of

bull loosely packed thymic epithelial cells loosely packed thymic epithelial cells bull interdigitating dendritic cells interdigitating dendritic cells bull macrophages macrophages

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 32: Functional organization of the Immune System

bull The secondary lymphoid organs include lymph nodes The secondary lymphoid organs include lymph nodes and the spleen as well as lymphoid tissues and the spleen as well as lymphoid tissues

bull The lymphoid tissues include The lymphoid tissues include the tonsils the the tonsils the appendix the Peyers patchesappendix the Peyers patches in the lining of the in the lining of the small intestines (small intestines (gut-associated lymphoid tissue or gut-associated lymphoid tissue or GALTGALT) )

bull The lymphoid tissue found beneath the mucous The lymphoid tissue found beneath the mucous membranes of the bronchi (membranes of the bronchi (bronchial-associated bronchial-associated lymphoid tissue or BALTlymphoid tissue or BALT) )

bull The lymphatic tissue found in the mucous The lymphatic tissue found in the mucous membranes (membranes (mucosa-associated lymphoid tissue or mucosa-associated lymphoid tissue or MALTMALT))

bull The lymphatic tissue found beneath the skin (The lymphatic tissue found beneath the skin (skin-skin-associated lymphoid tissue or SALTassociated lymphoid tissue or SALT) )

Primary and SecondaryPrimary and Secondary Lymphoid organs Lymphoid organs

Primarycentral lymphoid Primarycentral lymphoid organs organs

BONE MARROWBONE MARROW is a central organ is a central organ where all the immune cells are where all the immune cells are born and only B cells mature born and only B cells mature (process termed as (process termed as B B lymphopoiesis) lymphopoiesis)

THYMUSTHYMUS is the other central organ is the other central organ in which T cells mature (in which T cells mature (T T lymphopoiesislymphopoiesis) )

The bone marrowThe bone marrow

Bone marrow is a spongy tissue found Bone marrow is a spongy tissue found within boneswithin bonesAll blood cells are produced within the bone All blood cells are produced within the bone marrowmarrowThe bone marrow of an adult produce about The bone marrow of an adult produce about three million red blood cells and 120000 three million red blood cells and 120000 white blood cells every second white blood cells every second All these cells originate from a small All these cells originate from a small population of stem cells which may be as population of stem cells which may be as few as one in a million of the bone marrow few as one in a million of the bone marrow cells cells

ThymuThymuss

bullThe thymus is an organ located in the The thymus is an organ located in the upper chestupper chest bullImmature lymphocytes leave the bone Immature lymphocytes leave the bone marrow and find their way to the thymus marrow and find their way to the thymus where they are ldquoeducatedrdquo to become where they are ldquoeducatedrdquo to become mature T-lymphocytesmature T-lymphocytes

ThymusThymusFlat bilobed organ situated above the heart Flat bilobed organ situated above the heart

and below the thyroid glandand below the thyroid gland Each lobe is surrounded by a capsule and is Each lobe is surrounded by a capsule and is

divided into lobules divided into lobules The lobules are separated from each other by The lobules are separated from each other by

strands of connective tissue called strands of connective tissue called trabeculaetrabeculae

Each lobule is organized into two Each lobule is organized into two compartments the compartments the cortex cortex (outer (outer compartment) the compartment) the medullamedulla (inner (inner compartment) compartment)

bull Cortex and Medulla are both crisscrossed by Cortex and Medulla are both crisscrossed by a a network of stromal cellsnetwork of stromal cells composed of composed of

bull loosely packed thymic epithelial cells loosely packed thymic epithelial cells bull interdigitating dendritic cells interdigitating dendritic cells bull macrophages macrophages

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 33: Functional organization of the Immune System

Primary and SecondaryPrimary and Secondary Lymphoid organs Lymphoid organs

Primarycentral lymphoid Primarycentral lymphoid organs organs

BONE MARROWBONE MARROW is a central organ is a central organ where all the immune cells are where all the immune cells are born and only B cells mature born and only B cells mature (process termed as (process termed as B B lymphopoiesis) lymphopoiesis)

THYMUSTHYMUS is the other central organ is the other central organ in which T cells mature (in which T cells mature (T T lymphopoiesislymphopoiesis) )

The bone marrowThe bone marrow

Bone marrow is a spongy tissue found Bone marrow is a spongy tissue found within boneswithin bonesAll blood cells are produced within the bone All blood cells are produced within the bone marrowmarrowThe bone marrow of an adult produce about The bone marrow of an adult produce about three million red blood cells and 120000 three million red blood cells and 120000 white blood cells every second white blood cells every second All these cells originate from a small All these cells originate from a small population of stem cells which may be as population of stem cells which may be as few as one in a million of the bone marrow few as one in a million of the bone marrow cells cells

ThymuThymuss

bullThe thymus is an organ located in the The thymus is an organ located in the upper chestupper chest bullImmature lymphocytes leave the bone Immature lymphocytes leave the bone marrow and find their way to the thymus marrow and find their way to the thymus where they are ldquoeducatedrdquo to become where they are ldquoeducatedrdquo to become mature T-lymphocytesmature T-lymphocytes

ThymusThymusFlat bilobed organ situated above the heart Flat bilobed organ situated above the heart

and below the thyroid glandand below the thyroid gland Each lobe is surrounded by a capsule and is Each lobe is surrounded by a capsule and is

divided into lobules divided into lobules The lobules are separated from each other by The lobules are separated from each other by

strands of connective tissue called strands of connective tissue called trabeculaetrabeculae

Each lobule is organized into two Each lobule is organized into two compartments the compartments the cortex cortex (outer (outer compartment) the compartment) the medullamedulla (inner (inner compartment) compartment)

bull Cortex and Medulla are both crisscrossed by Cortex and Medulla are both crisscrossed by a a network of stromal cellsnetwork of stromal cells composed of composed of

bull loosely packed thymic epithelial cells loosely packed thymic epithelial cells bull interdigitating dendritic cells interdigitating dendritic cells bull macrophages macrophages

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 34: Functional organization of the Immune System

Primarycentral lymphoid Primarycentral lymphoid organs organs

BONE MARROWBONE MARROW is a central organ is a central organ where all the immune cells are where all the immune cells are born and only B cells mature born and only B cells mature (process termed as (process termed as B B lymphopoiesis) lymphopoiesis)

THYMUSTHYMUS is the other central organ is the other central organ in which T cells mature (in which T cells mature (T T lymphopoiesislymphopoiesis) )

The bone marrowThe bone marrow

Bone marrow is a spongy tissue found Bone marrow is a spongy tissue found within boneswithin bonesAll blood cells are produced within the bone All blood cells are produced within the bone marrowmarrowThe bone marrow of an adult produce about The bone marrow of an adult produce about three million red blood cells and 120000 three million red blood cells and 120000 white blood cells every second white blood cells every second All these cells originate from a small All these cells originate from a small population of stem cells which may be as population of stem cells which may be as few as one in a million of the bone marrow few as one in a million of the bone marrow cells cells

ThymuThymuss

bullThe thymus is an organ located in the The thymus is an organ located in the upper chestupper chest bullImmature lymphocytes leave the bone Immature lymphocytes leave the bone marrow and find their way to the thymus marrow and find their way to the thymus where they are ldquoeducatedrdquo to become where they are ldquoeducatedrdquo to become mature T-lymphocytesmature T-lymphocytes

ThymusThymusFlat bilobed organ situated above the heart Flat bilobed organ situated above the heart

and below the thyroid glandand below the thyroid gland Each lobe is surrounded by a capsule and is Each lobe is surrounded by a capsule and is

divided into lobules divided into lobules The lobules are separated from each other by The lobules are separated from each other by

strands of connective tissue called strands of connective tissue called trabeculaetrabeculae

Each lobule is organized into two Each lobule is organized into two compartments the compartments the cortex cortex (outer (outer compartment) the compartment) the medullamedulla (inner (inner compartment) compartment)

bull Cortex and Medulla are both crisscrossed by Cortex and Medulla are both crisscrossed by a a network of stromal cellsnetwork of stromal cells composed of composed of

bull loosely packed thymic epithelial cells loosely packed thymic epithelial cells bull interdigitating dendritic cells interdigitating dendritic cells bull macrophages macrophages

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 35: Functional organization of the Immune System

The bone marrowThe bone marrow

Bone marrow is a spongy tissue found Bone marrow is a spongy tissue found within boneswithin bonesAll blood cells are produced within the bone All blood cells are produced within the bone marrowmarrowThe bone marrow of an adult produce about The bone marrow of an adult produce about three million red blood cells and 120000 three million red blood cells and 120000 white blood cells every second white blood cells every second All these cells originate from a small All these cells originate from a small population of stem cells which may be as population of stem cells which may be as few as one in a million of the bone marrow few as one in a million of the bone marrow cells cells

ThymuThymuss

bullThe thymus is an organ located in the The thymus is an organ located in the upper chestupper chest bullImmature lymphocytes leave the bone Immature lymphocytes leave the bone marrow and find their way to the thymus marrow and find their way to the thymus where they are ldquoeducatedrdquo to become where they are ldquoeducatedrdquo to become mature T-lymphocytesmature T-lymphocytes

ThymusThymusFlat bilobed organ situated above the heart Flat bilobed organ situated above the heart

and below the thyroid glandand below the thyroid gland Each lobe is surrounded by a capsule and is Each lobe is surrounded by a capsule and is

divided into lobules divided into lobules The lobules are separated from each other by The lobules are separated from each other by

strands of connective tissue called strands of connective tissue called trabeculaetrabeculae

Each lobule is organized into two Each lobule is organized into two compartments the compartments the cortex cortex (outer (outer compartment) the compartment) the medullamedulla (inner (inner compartment) compartment)

bull Cortex and Medulla are both crisscrossed by Cortex and Medulla are both crisscrossed by a a network of stromal cellsnetwork of stromal cells composed of composed of

bull loosely packed thymic epithelial cells loosely packed thymic epithelial cells bull interdigitating dendritic cells interdigitating dendritic cells bull macrophages macrophages

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 36: Functional organization of the Immune System

ThymuThymuss

bullThe thymus is an organ located in the The thymus is an organ located in the upper chestupper chest bullImmature lymphocytes leave the bone Immature lymphocytes leave the bone marrow and find their way to the thymus marrow and find their way to the thymus where they are ldquoeducatedrdquo to become where they are ldquoeducatedrdquo to become mature T-lymphocytesmature T-lymphocytes

ThymusThymusFlat bilobed organ situated above the heart Flat bilobed organ situated above the heart

and below the thyroid glandand below the thyroid gland Each lobe is surrounded by a capsule and is Each lobe is surrounded by a capsule and is

divided into lobules divided into lobules The lobules are separated from each other by The lobules are separated from each other by

strands of connective tissue called strands of connective tissue called trabeculaetrabeculae

Each lobule is organized into two Each lobule is organized into two compartments the compartments the cortex cortex (outer (outer compartment) the compartment) the medullamedulla (inner (inner compartment) compartment)

bull Cortex and Medulla are both crisscrossed by Cortex and Medulla are both crisscrossed by a a network of stromal cellsnetwork of stromal cells composed of composed of

bull loosely packed thymic epithelial cells loosely packed thymic epithelial cells bull interdigitating dendritic cells interdigitating dendritic cells bull macrophages macrophages

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 37: Functional organization of the Immune System

ThymusThymusFlat bilobed organ situated above the heart Flat bilobed organ situated above the heart

and below the thyroid glandand below the thyroid gland Each lobe is surrounded by a capsule and is Each lobe is surrounded by a capsule and is

divided into lobules divided into lobules The lobules are separated from each other by The lobules are separated from each other by

strands of connective tissue called strands of connective tissue called trabeculaetrabeculae

Each lobule is organized into two Each lobule is organized into two compartments the compartments the cortex cortex (outer (outer compartment) the compartment) the medullamedulla (inner (inner compartment) compartment)

bull Cortex and Medulla are both crisscrossed by Cortex and Medulla are both crisscrossed by a a network of stromal cellsnetwork of stromal cells composed of composed of

bull loosely packed thymic epithelial cells loosely packed thymic epithelial cells bull interdigitating dendritic cells interdigitating dendritic cells bull macrophages macrophages

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 38: Functional organization of the Immune System

ThymusThymusbull In the cortex the network is densely packed with In the cortex the network is densely packed with

thymocytes thymocytes Cells are less dense in medullaCells are less dense in medulla bull In medulla the epithelial cells are more visible In medulla the epithelial cells are more visible

and and HASSALs Corpuscles are presentHASSALs Corpuscles are present (Function (Function Unknown) Unknown)

bull The thymus is at its lThe thymus is at its largest relative size at birthargest relative size at birth and its land its largest actual size is at pubertyargest actual size is at puberty

bull After puberty the thymus begins to shrink In After puberty the thymus begins to shrink In elderly individuals it is usually less than 3 grams elderly individuals it is usually less than 3 grams in weight in weight

bull There is relationship between aging and a decline There is relationship between aging and a decline in immune responsiveness in immune responsiveness

bull Stress can also result in shrinkage of the thymus Stress can also result in shrinkage of the thymus

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 39: Functional organization of the Immune System

ThymusThymusbull Precursor T cells enter thymus from the Precursor T cells enter thymus from the

blood (blood (there are no afferent lymphatic there are no afferent lymphatic vesselsvessels] and mature into functional T ] and mature into functional T lymphocyteslymphocytes

bull However the vast majority of these cells However the vast majority of these cells are destined to die due to (APOPTOSIS) - are destined to die due to (APOPTOSIS) - programmed cell deathprogrammed cell death

bull The T cells (thymocytes) go through a The T cells (thymocytes) go through a selection process in the thymus based selection process in the thymus based upon the TcR that they possess upon the TcR that they possess

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 40: Functional organization of the Immune System

Process of thymic educationProcess of thymic educationbull The complete process of thymic education is a The complete process of thymic education is a

two-step process in which Thymic cortical two-step process in which Thymic cortical epithelial cells function as the effector cells in a epithelial cells function as the effector cells in a process known as process known as POSITIVE SELECTIONPOSITIVE SELECTION

bull In positive selection T cells which bear a TcR In positive selection T cells which bear a TcR which which can bindcan bind SELF-MHC are selected to survive SELF-MHC are selected to survive and proliferate Cells which are not positively and proliferate Cells which are not positively selected are triggered to undergo APOPTOSIS selected are triggered to undergo APOPTOSIS

bull Positively selected thymocytes must go through a Positively selected thymocytes must go through a second phase of selection known as second phase of selection known as NEGATIVE NEGATIVE SELECTIONSELECTION

bull Functionally during negative selection any T cell Functionally during negative selection any T cell that is presented antigen + MHC within the that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS thymus is triggered to undergo APOPTOSIS

bull Most importantly thymic macrophages and Most importantly thymic macrophages and dendritic cells serve as APCs in the process of dendritic cells serve as APCs in the process of negative selection negative selection

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 41: Functional organization of the Immune System

Thymic hormones Thymic hormones

bull Stromal cells secrete soluble factors Stromal cells secrete soluble factors which are important in T cell maturation which are important in T cell maturation

bull Some examples includeSome examples include alpha- 1- thymosin alpha- 1- thymosin beta - 4- thymosin beta - 4- thymosin thymopoietin thymopoietin thymulin thymulin

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 42: Functional organization of the Immune System

Lymph nodesLymph nodesbull Small bean-shaped Small bean-shaped lymph nodes lymph nodes are laced are laced

along the lymphatic vessels with clusters along the lymphatic vessels with clusters in the neck armpits abdomen and groinin the neck armpits abdomen and groin

bull Each lymph node contains specialized Each lymph node contains specialized compartments where immune cells compartments where immune cells congregate and where they can encounter congregate and where they can encounter antigensantigens

bull Immune cells and foreign particles enter Immune cells and foreign particles enter the lymph nodes via incoming lymphatic the lymph nodes via incoming lymphatic vessels All lymphocytes exit lymph nodes vessels All lymphocytes exit lymph nodes through outgoing lymphatic vesselsthrough outgoing lymphatic vessels

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 43: Functional organization of the Immune System

Lymph NodeLymph Node

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 44: Functional organization of the Immune System

The regions of Lymph The regions of Lymph nodenode

3 regions to the lymph node 3 regions to the lymph node bull CortexCortex (outermost layer- (outermost layer- contains mostly B contains mostly B

lymphocyteslymphocytes plus both follicular dendritic cells and plus both follicular dendritic cells and macrophages all arranged in clusters called macrophages all arranged in clusters called primary primary folliclesfollicles))

bull Following antigenic stimulation the primary Following antigenic stimulation the primary follicles become follicles become secondary folliclessecondary follicles consisting of consisting of concentric rings of densely packed lymphocytes concentric rings of densely packed lymphocytes and central lymphocytes macrophages and and central lymphocytes macrophages and dendritic cells dendritic cells

bull The The GCs (germinal centers)GCs (germinal centers) contain large contain large proliferating B lymphocytes and plasma cells proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells interspersed with macrophages and dendritic cells

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 45: Functional organization of the Immune System

The regions of Lymph The regions of Lymph nodenode

bull The GC is a site of intense B-Cell activation and The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory differentiation into plasma cells and memory cellscells

bull ParacortexParacortex - (layer just beneath the cortex) This - (layer just beneath the cortex) This region is sometimes called the T dependent region is sometimes called the T dependent region of the lymph node region of the lymph node It is an area populated with T lymphocytes and It is an area populated with T lymphocytes and also interdigitating dendritic cells It is an also interdigitating dendritic cells It is an important site for T cell activation by these APCs important site for T cell activation by these APCs

bull MedullaMedulla- inner most region more sparsely - inner most region more sparsely populated by cells Many of the cells are plasma populated by cells Many of the cells are plasma cells activated Th and Tc are also present In cells activated Th and Tc are also present In addition there is a high concentration of addition there is a high concentration of immunoglobulin in this region due to the large immunoglobulin in this region due to the large population of plasma cells population of plasma cells

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 46: Functional organization of the Immune System

Swelling of lymph nodes Swelling of lymph nodes

bull This huge increase in the number of This huge increase in the number of lymphocytes is due tolymphocytes is due to

bull proliferation of lymphocytes within the lymph proliferation of lymphocytes within the lymph node node

bull influx of lymphocytes from the circulatory influx of lymphocytes from the circulatory system system

bull -Clearly the concentration of lymphocytes in -Clearly the concentration of lymphocytes in the lymph nodes can increase greatly the lymph nodes can increase greatly following antigenic stimulation accounting for following antigenic stimulation accounting for swelling of lymph nodesswelling of lymph nodes

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 47: Functional organization of the Immune System

The spleenThe spleenbull The spleen is the largest of the The spleen is the largest of the

lymphoid organs lymphoid organs bull The The spleen spleen is a flattened organ at the is a flattened organ at the

upper left of the abdomen upper left of the abdomen bull Like the lymph nodes the spleen Like the lymph nodes the spleen

contains specialized compartments contains specialized compartments where immune cells gather and work where immune cells gather and work and serves as a meeting ground where and serves as a meeting ground where immune defenses confront antigensimmune defenses confront antigens

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 48: Functional organization of the Immune System

SpleenSpleen

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 49: Functional organization of the Immune System

SpleenSpleen

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 50: Functional organization of the Immune System

Spleen Spleen

bull The spleen is adapted The spleen is adapted to filter theto filter the bloodblood it responds therefore to it responds therefore to systemic systemic infectionsinfections

bull It is surrounded by a capsule which It is surrounded by a capsule which sends trabeculae into the interior to sends trabeculae into the interior to form a compartmentalized structure form a compartmentalized structure There are two types of compartments There are two types of compartments [[Red PulpRed Pulp and and White PulpWhite Pulp] ]

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 51: Functional organization of the Immune System

Spleen Spleen bull Red Pulp-Red Pulp- Network of sinusoids populated with Network of sinusoids populated with

macrophages and numerous erythrocytes Site macrophages and numerous erythrocytes Site where old RBCs are destroyed and removed where old RBCs are destroyed and removed

bull White Pulp-White Pulp- Surrounds the splenic arteries Surrounds the splenic arteries forming a periarteriolar lymphoid sheath (PALS) forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes populated mainly by T lymphocytes

bull Clusters of B lymphocytes in the White Pulp form Clusters of B lymphocytes in the White Pulp form primary folliclesprimary follicles occupying a more peripheral occupying a more peripheral positionposition

bull Upon antigenic challenge these primary follicles Upon antigenic challenge these primary follicles develop into characteristic develop into characteristic secondary folliclessecondary follicles containing containing germinal centersgerminal centers

bull The spleen is The spleen is NOT supplied by afferent lymphaticsNOT supplied by afferent lymphatics

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 52: Functional organization of the Immune System

Functions of the SpleenFunctions of the Spleenbull The spleen functions both as immune and The spleen functions both as immune and

hematopoietic systemshematopoietic systemsThe The immune functions include immune functions include

bull proliferation of lymphocytes proliferation of lymphocytes bull production of humoral antibodies production of humoral antibodies bull removal of macromolecular antigens from the blood removal of macromolecular antigens from the blood

The hematopoietic functions includeThe hematopoietic functions includebull formation of blood cells in fetal life formation of blood cells in fetal life bull removal and destruction of senile damaged and removal and destruction of senile damaged and

abnormal RBCs and platelets abnormal RBCs and platelets bull retrieval of the iron from hemoglobin retrieval of the iron from hemoglobin bull storage of blood in some species (not humans) storage of blood in some species (not humans)

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 53: Functional organization of the Immune System

Lymphoid tissuesLymphoid tissues

bull Clumps of lymphoid tissue are Clumps of lymphoid tissue are found in many parts of the body found in many parts of the body especially in the linings of the especially in the linings of the digestive tract and the airways and digestive tract and the airways and lungsmdashterritories that serve as lungsmdashterritories that serve as gateways to the body These gateways to the body These tissues include the tissues include the tonsilstonsils adenoidsadenoids and and appendixappendix

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 54: Functional organization of the Immune System

Peyers patchesPeyers patchesPeyers patches are areas of lymphoid Peyers patches are areas of lymphoid

tissue located in the wall of the intestine tissue located in the wall of the intestine and in some mammalian species such as and in some mammalian species such as sheep cattle and rabbitssheep cattle and rabbits

Peyers patches have a function similar to Peyers patches have a function similar to the bursa of fabricius of birds and bone the bursa of fabricius of birds and bone marrow of other mammals marrow of other mammals B cell B cell differentiation and maturationdifferentiation and maturation

bull Actually Two types of Peyers patches Actually Two types of Peyers patches seem to occur one with primary lymphoid seem to occur one with primary lymphoid function and another with secondary function and another with secondary lymphoid function lymphoid function

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 55: Functional organization of the Immune System

Functions of lymphatic organsFunctions of lymphatic organs

11 GenerateGenerate immuno-competant immuno-competant lymphocyteslymphocytes

22 Concentrate antigensConcentrate antigens into lymphoid into lymphoid organsorgans

33 Circulate lymphocytesCirculate lymphocytes through through lymphoid organs exposing antigen lymphoid organs exposing antigen to a variety of lymphocytesto a variety of lymphocytes

44 Deliver antibodiesDeliver antibodies and effector T and effector T cells to the blood and tissuescells to the blood and tissues

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 56: Functional organization of the Immune System

Kinds of Adaptive Kinds of Adaptive immunityimmunity

bullAdaptive immune responses Adaptive immune responses are actually reactions of the are actually reactions of the immune system to immune system to antigensantigens

bull There are two types of There are two types of adaptive immune responsesadaptive immune responses

bull Humoral and cell Humoral and cell mediatedmediated

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 57: Functional organization of the Immune System

Adaptive Humoral immunityAdaptive Humoral immunity

bull During humoral immune responsesDuring humoral immune responses proteinsproteins called called antibodiesantibodies destroy destroy antigens appear in the blood and other antigens appear in the blood and other body fluids body fluids

bull Humoral immune responses resist invaders Humoral immune responses resist invaders that act outside of cells such as bacteria that act outside of cells such as bacteria and and toxinstoxins (poisonous substances produced (poisonous substances produced by living organisms) by living organisms)

bull Humoral immune responses can also Humoral immune responses can also prevent viruses from entering cellsprevent viruses from entering cells

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 58: Functional organization of the Immune System

Adaptive cellular immunityAdaptive cellular immunity

bull During During cell-mediated immune responsescell-mediated immune responses cells that can destroy other cells that are cells that can destroy other cells that are either infected with or producing a specific either infected with or producing a specific antigen antigen

bull Cell-mediated immune responses resist Cell-mediated immune responses resist invaders that reproduce within the body invaders that reproduce within the body cells such as virusescells such as viruses

bull Cell-mediated responses may also destroy Cell-mediated responses may also destroy cells making cells making mutatedmutated (changed) forms of (changed) forms of normal molecules as in some cancersnormal molecules as in some cancers

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 59: Functional organization of the Immune System

Immunity is a coordinated effort Immunity is a coordinated effort by the bodyby the body

bull bull It was previously believed that the immune It was previously believed that the immune system functioned independently in the bodysystem functioned independently in the body

bull Itrsquos now known that there are several links Itrsquos now known that there are several links between the immune nervous and endocrine between the immune nervous and endocrine systemssystems

bull Certain immune responses trigger endocrine Certain immune responses trigger endocrine ampor nervous activityampor nervous activity

bull Lymphocytes amp macrophages are responsive to Lymphocytes amp macrophages are responsive to signals from the nervous system and certain signals from the nervous system and certain endocrine glandsendocrine glands

bull Therefore immunity is the job of the entire Therefore immunity is the job of the entire body not just one systembody not just one system

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 60: Functional organization of the Immune System

About the presenterAbout the presenterbull DrBVictor is a highly experienced postgraduate DrBVictor is a highly experienced postgraduate

biology teacher recently retired from the reputed biology teacher recently retired from the reputed educational institution St Xavierrsquo s College educational institution St Xavierrsquo s College Palayamkottai India-627001Presently HOD of Biotech Palayamkottai India-627001Presently HOD of Biotech at Annai Velankanni college Tholayavattam K K Distat Annai Velankanni college Tholayavattam K K Dist

bull He was the dean of sciences and assistant controller of He was the dean of sciences and assistant controller of examinations of St Xavierrsquos collegeexaminations of St Xavierrsquos college

bull He has more than 32 years of teaching and research He has more than 32 years of teaching and research experience and has guided more than 12 Ph D experience and has guided more than 12 Ph D scholarsscholars

bull He has taught Immunology and biochemistry to He has taught Immunology and biochemistry to graduate and post graduate studentsgraduate and post graduate students

bull Send your comments to bonfiliusvictorgmailcomSend your comments to bonfiliusvictorgmailcom

Page 61: Functional organization of the Immune System